From 6b34fb5252112951868dec30e5ca083288cbd04b Mon Sep 17 00:00:00 2001 From: Xiang Li Date: Tue, 6 May 2025 10:49:37 -0400 Subject: [PATCH] Add potential CTNNB1 from msk-impact --- VUEs.txt | 86 + generated/VUEs.json | 10758 +++++++++++++++++++++++++++++++----------- 2 files changed, 7987 insertions(+), 2857 deletions(-) diff --git a/VUEs.txt b/VUEs.txt index dd9cc31..af1d39a 100644 --- a/VUEs.txt +++ b/VUEs.txt @@ -26,6 +26,92 @@ CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265648_41266493del 3,41265648,41266493,CCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGC,- ENST00000349496 ENST00000349496.5:c.13+76_290del p.X5_splice Splice_Site p.A5_A97del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265674_41266212del 3,41265674,41266212,TTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATT,- ENST00000349496 ENST00000349496.5:c.13+104_211del p.X5_splice Splice_Site p.A5_F70del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265990_41266204del 3,41265990,41266204,AATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAA,- ENST00000349496 ENST00000349496.5:c.14-27_201del p.X5_splice Splice_Site p.A5_Q68del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265567_41266214del 3,41265567,41266214,CTCAAGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTT,- ENST00000349496 ENST00000349496.5:c.12_215del X4_splice Splice_Site p.T3_S71del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265567_41266492del 3,41265567,41266492,CTCAAGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTG,- ENST00000349496 ENST00000349496.5:c.10_291del X4_splice Splice_Site p.T3_A97del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265911_41266366del 3,41265911,41266366,ACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAA,- ENST00000349496 ENST00000349496.5:c.14-106_162del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265933_41266400del 3,41265933,41266400,AATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAG,- ENST00000349496 ENST00000349496.5:c.14-84_184del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265619_41266368del 3,41265619,41266368,TTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGG,- ENST00000349496 ENST00000349496.5:c.13+47_14-144del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265970_41266028del 3,41265970,41266028,AGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGG,- ENST00000349496 ENST00000349496.5:c.14-44_28del X5_splice Splice_Site p.A5_E9del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265915_41266316del 3,41265915,41266316,TATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGG,- ENST00000349496 ENST00000349496.5:c.14-102_166del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265584_41266314del 3,41265584,41266314,TAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTA,- ENST00000349496 ENST00000349496.5:c.13+12_14-179del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265684_41266624del 3,41265684,41266624,ACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGG,- ENST00000349496 ENST00000349496.5:c.13+112_14-79del X5_splice Splice_Site p.A5_N141del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265696_41266154del 3,41265696,41266154,ATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGA,- ENST00000349496 ENST00000349496.5:c.13+124_14-67del X5_splice Splice_Site p.A5_N51del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265771_41266375del 3,41265771,41266375,GCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGA,- ENST00000349496 ENST00000349496.5:c.13+199_22del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266000_41266175del 3,41266000,41266175,CTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGG,- ENST00000349496 ENST00000349496.5:c.14-17_172del X5_splice Splice_Site p.A5_D58del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265882_41266241del 3,41265882,41266241,CTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTT,- ENST00000349496 ENST00000349496.5:c.14-133_135del X5_splice Splice_Site p.A5_A80del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265762_41266317del 3,41265762,41266317,TGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAG,- ENST00000349496 ENST00000349496.5:c.13+190_14-1del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265982_41266276del 3,41265982,41266276,AATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACA,- ENST00000349496 ENST00000349496.5:c.14-34_234del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265789_41266324del 3,41265789,41266324,CAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCA,- ENST00000349496 ENST00000349496.5:c.13+217_40del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265805_41266404del 3,41265805,41266404,CTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAA,- ENST00000349496 ENST00000349496.5:c.14-212_56del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265687_41266331del 3,41265687,41266331,TTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCA,- ENST00000349496 ENST00000349496.5:c.13+116_14-75del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265901_41266287del 3,41265901,41266287,TTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAA,- ENST00000349496 ENST00000349496.5:c.14-115_153del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265743_41266365del 3,41265743,41266365,CACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGT,- ENST00000349496 ENST00000349496.5:c.13+174_242-77del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265906_41266360del 3,41265906,41266360,ATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGC,- ENST00000349496 ENST00000349496.5:c.14-110_242-84del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265718_41266423del 3,41265718,41266423,TGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAG,- ENST00000349496 ENST00000349496.5:c.13+148_242-20del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265989_41266510del 3,41265989,41266510,TAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACAT,- ENST00000349496 ENST00000349496.5:c.14-26_309del X5_splice Splice_Site p.A5_L103del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266002_41266229del 3,41266002,41266229,GTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTC,- ENST00000349496 ENST00000349496.5:c.14-15_226del X5_splice Splice_Site p.A5_Q76del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265988_41266211del 3,41265988,41266211,CTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGAT,- ENST00000349496 ENST00000349496.5:c.14-29_208del X5_splice Splice_Site p.A5_F70del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265592_41266289del 3,41265592,41266289,TAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAG,- ENST00000349496 ENST00000349496.5:c.13+21_241+46del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265880_41266334del 3,41265880,41266334,TTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGT,- ENST00000349496 ENST00000349496.5:c.14-136_241+91del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266015_41266600del 3,41266015,41266600,AGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGA,- ENST00000349496 ENST00000349496.5:c.14-1_398del X5_splice Splice_Site p.A5_K133del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265810_41266364del 3,41265810,41266364,TCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATG,- ENST00000349496 ENST00000349496.5:c.14-204_242-78del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265989_41266253del 3,41265989,41266253,TAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTA,- ENST00000349496 ENST00000349496.5:c.14-27_241+10del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265648_41266274del 3,41265648,41266274,CCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTG,- ENST00000349496 ENST00000349496.5:c.13+76_241+30del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265739_41266347del 3,41265739,41266347,AAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAA,- ENST00000349496 ENST00000349496.5:c.13+168_242-97del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265621_41266305del 3,41265621,41266305,GCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAA,- ENST00000349496 ENST00000349496.5:c.13+50_241+62del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265955_41266414del 3,41265955,41266414,TTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTG,- ENST00000349496 ENST00000349496.5:c.14-62_242-31del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265625_41266067del 3,41265625,41266067,TTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTG,- ENST00000349496 ENST00000349496.5:c.13+56_67del X5_splice Splice_Site p.A5_V22del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265977_41266368del 3,41265977,41266368,TTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCAC,- ENST00000349496 ENST00000349496.5:c.14-37_242-74del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265922_41266247del 3,41265922,41266247,AAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTA,- ENST00000349496 ENST00000349496.5:c.14-94_241+4del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265888_41266277del 3,41265888,41266277,TTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAA,- ENST00000349496 ENST00000349496.5:c.14-129_241+33del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265782_41266409del 3,41265782,41266409,CTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAA,- ENST00000349496 ENST00000349496.5:c.13+213_242-33del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265591_41266253del 3,41265591,41266253,TTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTA,- ENST00000349496 ENST00000349496.5:c.13+22_241+12del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266007_41266408del 3,41266007,41266408,GTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGA,- ENST00000349496 ENST00000349496.5:c.14-10_242-37del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265823_41266422del 3,41265823,41266422,GTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGA,- ENST00000349496 ENST00000349496.5:c.14-192_242-21del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265947_41266244del 3,41265947,41266244,CAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTG,- ENST00000349496 ENST00000349496.5:c.14-70_241del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265921_41266361del 3,41265921,41266361,TAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCA,- ENST00000349496 ENST00000349496.5:c.14-96_242-84del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265792_41266371del 3,41265792,41266371,TACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTT,- ENST00000349496 ENST00000349496.5:c.14-218_242-67del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265957_41266436del 3,41265957,41266436,TTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACC,- ENST00000349496 ENST00000349496.5:c.14-56_242-5del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265946_41266408del 3,41265946,41266408,ACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGA,- ENST00000349496 ENST00000349496.5:c.14-69_242-35del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265991_41266603del 3,41265991,41266603,ATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAAC,- ENST00000349496 ENST00000349496.5:c.14-22_404del X5_splice Splice_Site p.A5_H134del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265757_41266254del 3,41265757,41266254,TAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTAT,- ENST00000349496 ENST00000349496.5:c.13+187_241+12del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265954_41266315del 3,41265954,41266315,TTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTAT,- ENST00000349496 ENST00000349496.5:c.14-63_241+71del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265647_41266373del 3,41265647,41266373,CCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTA,- ENST00000349496 ENST00000349496.5:c.13+77_242-70del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265747_41266399del 3,41265747,41266399,AGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGT,- ENST00000349496 ENST00000349496.5:c.13+176_242-45del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265879_41266283del 3,41265879,41266283,ATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGA,- ENST00000349496 ENST00000349496.5:c.14-136_241+41del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265913_41266289del 3,41265913,41266289,TTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAG,- ENST00000349496 ENST00000349496.5:c.14-101_241+48del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265761_41266271del 3,41265761,41266271,CTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTA,- ENST00000349496 ENST00000349496.5:c.13+192_241+30del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265965_41266375del 3,41265965,41266375,ATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACC,- ENST00000349496 ENST00000349496.5:c.14-49_242-67del X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265859_41266211del 3,41265859,41266211,CTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGAT,- ENST00000349496 ENST00000349496.5:c.14-158_208del X5_splice Splice_Site p.A5_F70del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266018_41266622del 3,41266018,41266622,TGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGAT,- ENST00000349496 ENST00000349496.5:c.16_420del X6_splice Splice_Site p.A5_I140del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266017_41266367del 3,41266017,41266367,CTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCA,- ENST00000349496 ENST00000349496.5:c.16_242-76del X6_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266028_41266605del 3,41266028,41266605,GAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACAT,- ENST00000349496 ENST00000349496.5:c.26_403del X9_splice Splice_Site p.M8_H134del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266024_41266592del 3,41266024,41266592,GATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACA,- ENST00000349496 ENST00000349496.5:c.25_393del X9_splice Splice_Site p.L7_Q130del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266032_41266609del 3,41266032,41266609,TGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAG,- ENST00000349496 ENST00000349496.5:c.30_407del X10_splice Splice_Site p.L10_V136del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266031_41266617del 3,41266031,41266617,TTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAAC,- ENST00000349496 ENST00000349496.5:c.31_417del X11_splice Splice_Site p.E9_N138del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266037_41266620del 3,41266037,41266620,ATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTT,- ENST00000349496 ENST00000349496.5:c.34_241+47del X12_splice Splice_Site p.D11_L139del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266035_41266624del 3,41266035,41266624,ACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTA,- ENST00000349496 ENST00000349496.5:c.34_423del X12_splice Splice_Site p.D11_N141del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266041_41266672del 3,41266041,41266672,CCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCCTGAACTGA,- ENST00000349496 ENST00000349496.5:c.39_470del X13_splice Splice_Site p.A13_T157del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266038_41266669del 3,41266038,41266669,TGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCCTGAAC,- ENST00000349496 ENST00000349496.5:c.37_468del X13_splice Splice_Site p.M12_L156del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266041_41266373del 3,41266041,41266373,CCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGA,- ENST00000349496 ENST00000349496.5:c.38_241+51del X14_splice Splice_Site p.A13_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266043_41266623del 3,41266043,41266623,ATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATT,- ENST00000349496 ENST00000349496.5:c.41_421del X14_splice Splice_Site p.A13_I140del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266046_41266665del 3,41266046,41266665,GAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCCT,- ENST00000349496 ENST00000349496.5:c.47_466del X16_splice Splice_Site p.M14_P154del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266047_41266630del 3,41266047,41266630,AACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATC,- ENST00000349496 ENST00000349496.5:c.46_429del X16_splice Splice_Site p.E15_Q143del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266049_41266557del 3,41266049,41266557,CCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCAT,- ENST00000349496 ENST00000349496.5:c.48_356del X16_splice Splice_Site p.E15_H118del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266050_41266639del 3,41266050,41266639,CAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATG,- ENST00000349496 ENST00000349496.5:c.51_440del X17_splice Splice_Site p.P16_A146del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266051_41266631del 3,41266051,41266631,AGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCA,- ENST00000349496 ENST00000349496.5:c.51_431del X17_splice Splice_Site p.P16_Q143del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266053_41266624del 3,41266053,41266624,ACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTA,- ENST00000349496 ENST00000349496.5:c.52_423del X18_splice Splice_Site p.D17_N141del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266054_41266649del 3,41266054,41266649,CAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGC,- ENST00000349496 ENST00000349496.5:c.53_448del X18_splice Splice_Site p.D17_A149del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266059_41266307del 3,41266059,41266307,AAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGT,- ENST00000349496 ENST00000349496.5:c.56_241+63del X19_splice Splice_Site p.K19_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266057_41266652del 3,41266057,41266652,AAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCAC,- ENST00000349496 ENST00000349496.5:c.55_450del X19_splice Splice_Site p.R18_T150del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266061_41266656del 3,41266061,41266656,GCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGT,- ENST00000349496 ENST00000349496.5:c.60_455del X20_splice Splice_Site p.K19_R151del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266064_41266656del 3,41266064,41266656,GCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGT,- ENST00000349496 ENST00000349496.5:c.63_455del X21_splice Splice_Site p.A20_R151del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266065_41266501del 3,41266065,41266501,CTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCC,- ENST00000349496 ENST00000349496.5:c.65_301del X22_splice Splice_Site p.A21_P100del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266063_41266577del 3,41266063,41266577,GGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTT,- ENST00000349496 ENST00000349496.5:c.65_379del X22_splice Splice_Site p.A20_L125del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266074_41266266del 3,41266074,41266266,ACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTG,- ENST00000349496 ENST00000349496.5:c.71_241+22del X24_splice Splice_Site p.H24_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266072_41266664del 3,41266072,41266664,TCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCC,- ENST00000349496 ENST00000349496.5:c.70_462del X24_splice Splice_Site p.S23_P154del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266079_41266629del 3,41266079,41266629,CAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTAT,- ENST00000349496 ENST00000349496.5:c.78_428del X26_splice Splice_Site p.W25_Y142del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending +CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266086_41266249del 3,41266086,41266249,AGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAG,- ENST00000349496 ENST00000349496.5:c.86_241+8del X29_splice Splice_Site p.Q28_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE 0 Pending MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411926_116412083del 7,116411926,116412083,TACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATA,- ENST00000397752 ENST00000397752.3:c.2914_3028+43del p.X972_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 27343443 Schrock et al., 2014 MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411770_116412349del 7,116411770,116412349,AGATTGTCGTCGATTCTTGTGTGCTGTCTTATATGTAGTCCATAAAACCCATGAGTTCTGGGCACTGGGTCAAAGTCTCCTGGGGCCCATGATAGCCGTCTTTAACAAGCTCTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATATACCTCAGTGGGTTGTGACATTGTTGTTTATTTTTGGTTTTGCATTTATATTTTTATAAAAACCTAAAGGAAGTATTTACCTCTGCCAAGTAAGTATTTGACACAAAATTACATGGCTCTTAATTTTAAAAGAACCCATGTATATATTACATTATGATTTTAGAGTCCATAAGCTCTCATTTCACAAAAAGGTTAATTTGAGCAAAAGTAATTTGTTTATCATCTAAGTGCAATAGTAAGAAATTGCGAAGCTCTCTTTTACAATC,- ENST00000397752 ENST00000397752.3:c.2887+62_3028+306del p.X963_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 27343443 Schrock et al., 2014 MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411818_116412557del 7,116411818,116412557,CCATGAGTTCTGGGCACTGGGTCAAAGTCTCCTGGGGCCCATGATAGCCGTCTTTAACAAGCTCTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATATACCTCAGTGGGTTGTGACATTGTTGTTTATTTTTGGTTTTGCATTTATATTTTTATAAAAACCTAAAGGAAGTATTTACCTCTGCCAAGTAAGTATTTGACACAAAATTACATGGCTCTTAATTTTAAAAGAACCCATGTATATATTACATTATGATTTTAGAGTCCATAAGCTCTCATTTCACAAAAAGGTTAATTTGAGCAAAAGTAATTTGTTTATCATCTAAGTGCAATAGTAAGAAATTGCGAAGCTCTCTTTTACAATCCAGGAAGAGTTAAGTTACAAAATATACTTATTTAAATGTAAGTTGGAACTGCTACATTTTTTACCTGTTGAAGCCCAAACATTGAAATTATACTGTTAGTAATTCTTCGAAGTGTTTTCAATGAACTGTTAGTACACAGCCTTTTTCCCACCATATTCTAGGACTTGAATGTATTTTGAGACTTAGCCAAGGAAAACCTTCAATTATG,- ENST00000397752 ENST00000397752.3:c.2888-79_3028+520del p.X963_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 27343443 Schrock et al., 2014 diff --git a/generated/VUEs.json b/generated/VUEs.json index 788dbdf..b7036b1 100644 --- a/generated/VUEs.json +++ b/generated/VUEs.json @@ -1999,32 +1999,22 @@ } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "MET", - "transcriptId": "ENST00000397752", - "genomicLocationDescription": "Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del)", - "defaultEffect": "splice", - "comment": "Skipping of exon 14", - "context": "Actionable in NSCLC", - "revisedProteinEffects": [ + }, { - "variant": "7:g.116411926_116412083del", - "genomicLocation": "7,116411926,116412083,TACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATA,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X972_splice", + "variant": "3:g.41265567_41266214del", + "genomicLocation": "3,41265567,41266214,CTCAAGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X4_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D963_D1010del", + "revisedProteinEffect": "p.T3_S71del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2914_3028+43del", + "hgvsc": "ENST00000349496.5:c.12_215del", "confirmed": false, "references": [ { - "pubmedId": "27343443", - "referenceText": "Schrock et al., 2014" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { @@ -2034,7 +2024,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Hepatobiliary Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -2054,7 +2044,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Hepatobiliary Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -2074,29 +2064,29 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Hepatobiliary Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411770_116412349del", - "genomicLocation": "7,116411770,116412349,AGATTGTCGTCGATTCTTGTGTGCTGTCTTATATGTAGTCCATAAAACCCATGAGTTCTGGGCACTGGGTCAAAGTCTCCTGGGGCCCATGATAGCCGTCTTTAACAAGCTCTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATATACCTCAGTGGGTTGTGACATTGTTGTTTATTTTTGGTTTTGCATTTATATTTTTATAAAAACCTAAAGGAAGTATTTACCTCTGCCAAGTAAGTATTTGACACAAAATTACATGGCTCTTAATTTTAAAAGAACCCATGTATATATTACATTATGATTTTAGAGTCCATAAGCTCTCATTTCACAAAAAGGTTAATTTGAGCAAAAGTAATTTGTTTATCATCTAAGTGCAATAGTAAGAAATTGCGAAGCTCTCTTTTACAATC,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", + "variant": "3:g.41265567_41266492del", + "genomicLocation": "3,41265567,41266492,CTCAAGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X4_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D963_D1010del", + "revisedProteinEffect": "p.T3_A97del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2887+62_3028+306del", + "hgvsc": "ENST00000349496.5:c.10_291del", "confirmed": false, "references": [ { - "pubmedId": "27343443", - "referenceText": "Schrock et al., 2014" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { @@ -2106,7 +2096,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Glioma": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -2122,10 +2112,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -2144,40 +2136,38 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Glioma": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411818_116412557del", - "genomicLocation": "7,116411818,116412557,CCATGAGTTCTGGGCACTGGGTCAAAGTCTCCTGGGGCCCATGATAGCCGTCTTTAACAAGCTCTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATATACCTCAGTGGGTTGTGACATTGTTGTTTATTTTTGGTTTTGCATTTATATTTTTATAAAAACCTAAAGGAAGTATTTACCTCTGCCAAGTAAGTATTTGACACAAAATTACATGGCTCTTAATTTTAAAAGAACCCATGTATATATTACATTATGATTTTAGAGTCCATAAGCTCTCATTTCACAAAAAGGTTAATTTGAGCAAAAGTAATTTGTTTATCATCTAAGTGCAATAGTAAGAAATTGCGAAGCTCTCTTTTACAATCCAGGAAGAGTTAAGTTACAAAATATACTTATTTAAATGTAAGTTGGAACTGCTACATTTTTTACCTGTTGAAGCCCAAACATTGAAATTATACTGTTAGTAATTCTTCGAAGTGTTTTCAATGAACTGTTAGTACACAGCCTTTTTCCCACCATATTCTAGGACTTGAATGTATTTTGAGACTTAGCCAAGGAAAACCTTCAATTATG,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", + "variant": "3:g.41265911_41266366del", + "genomicLocation": "3,41265911,41266366,ACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D963_D1010del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-79_3028+520del", + "hgvsc": "ENST00000349496.5:c.14-106_162del", "confirmed": false, "references": [ { - "pubmedId": "27343443", - "referenceText": "Schrock et al., 2014" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -2192,12 +2182,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -2212,33 +2200,31 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411874_116411897del", - "genomicLocation": "7,116411874,116411897,ACAAGCTCTTTCTTTCTCTCTGTT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265933_41266400del", + "genomicLocation": "3,41265933,41266400,AATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-29_2888-6del", + "hgvsc": "ENST00000349496.5:c.14-84_184del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2288,23 +2274,23 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411881_116411897del", - "genomicLocation": "7,116411881,116411897,CTTTCTTTCTCTCTGTT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265619_41266368del", + "genomicLocation": "3,41265619,41266368,TTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-22_2888-6del", + "hgvsc": "ENST00000349496.5:c.13+47_14-144del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2354,32 +2340,34 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411881_116411937del", - "genomicLocation": "7,116411881,116411937,CTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGA,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", + "variant": "3:g.41265970_41266028del", + "genomicLocation": "3,41265970,41266028,AGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D963_D1010del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedProteinEffect": "p.A5_E9del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-22_2922del", + "hgvsc": "ENST00000349496.5:c.14-44_28del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Skin Cancer, Non-Melanoma": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -2394,10 +2382,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Skin Cancer, Non-Melanoma": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -2412,31 +2402,33 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Skin Cancer, Non-Melanoma": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411860_116411888del", - "genomicLocation": "7,116411860,116411888,GATAGCCGTCTTTAACAAGCTCTTTCTTT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.*963*", - "vepPredictedVariantClassification": "Intron", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265915_41266316del", + "genomicLocation": "3,41265915,41266316,TATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-43_2888-15del", + "hgvsc": "ENST00000349496.5:c.14-102_166del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2489,20 +2481,20 @@ "therapeuticLevel": null }, { - "variant": "7:g.116411879_116411896del", - "genomicLocation": "7,116411879,116411896,CTCTTTCTTTCTCTCTGT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265584_41266314del", + "genomicLocation": "3,41265584,41266314,TAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-24_2888-7del", + "hgvsc": "ENST00000349496.5:c.13+12_14-179del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2552,60 +2544,50 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116412046A>G", - "genomicLocation": "7,116412046,116412046,A,G", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X1010_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265684_41266624del", + "genomicLocation": "3,41265684,41266624,ACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_N141del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.3028+3A>G", + "hgvsc": "ENST00000349496.5:c.13+112_14-79del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 16, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 16 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 3, - "unknownVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 3 - }, - "unknownVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 40, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 2, - "Hepatobiliary Cancer": 1, - "Non-Small Cell Lung Cancer": 37 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -2620,37 +2602,31 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 45, - "unknownVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 2, - "Hepatobiliary Cancer": 1, - "Non-Small Cell Lung Cancer": 42 - }, - "unknownVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411879_116411897del", - "genomicLocation": "7,116411879,116411897,CTCTTTCTTTCTCTCTGTT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41265696_41266154del", + "genomicLocation": "3,41265696,41266154,ATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_N51del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-24_2888-6del", + "hgvsc": "ENST00000349496.5:c.13+124_14-67del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2700,23 +2676,23 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411887_116411906del", - "genomicLocation": "7,116411887,116411906,TTCTCTCTGTTTTAAGATCT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", + "variant": "3:g.41265771_41266375del", + "genomicLocation": "3,41265771,41266375,GCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D963_D1010del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-16_2891del", + "hgvsc": "ENST00000349496.5:c.13+199_22del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2766,40 +2742,35 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116412043G>A", - "genomicLocation": "7,116412043,116412043,G,A", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.D1010N", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.D963_D1010del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266000_41266175del", + "genomicLocation": "3,41266000,41266175,CTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D58del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.3028G>A", + "hgvsc": "ENST00000349496.5:c.14-17_172del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 38, - "unknownVariantsCount": 1, - "germlineVariantsCountByCancerType": {}, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 1, - "Glioma": 1, - "Non-Small Cell Lung Cancer": 35, - "Salivary Gland Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { @@ -2813,18 +2784,13 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 68, - "unknownVariantsCount": 1, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 2, - "Glioma": 1, - "Non-Small Cell Lung Cancer": 64, - "Salivary Gland Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, "tcga": { @@ -2838,38 +2804,33 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 72, - "unknownVariantsCount": 1, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 2, - "Glioma": 1, - "Non-Small Cell Lung Cancer": 68, - "Salivary Gland Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411885_116411897del", - "genomicLocation": "7,116411885,116411897,CTTTCTCTCTGTT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41265882_41266241del", + "genomicLocation": "3,41265882,41266241,CTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_A80del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-18_2888-6del", + "hgvsc": "ENST00000349496.5:c.14-133_135del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2919,23 +2880,23 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116412041_116412044del", - "genomicLocation": "7,116412041,116412044,AAGG,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X1009_splice", + "variant": "3:g.41265762_41266317del", + "genomicLocation": "3,41265762,41266317,TGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D963_D1010del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.3026_3028+1del", + "hgvsc": "ENST00000349496.5:c.13+190_14-1del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -2985,23 +2946,23 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411881_116411895del", - "genomicLocation": "7,116411881,116411895,CTTTCTTTCTCTCTG,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265982_41266276del", + "genomicLocation": "3,41265982,41266276,AATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-22_2888-8del", + "hgvsc": "ENST00000349496.5:c.14-34_234del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -3051,23 +3012,23 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411867_116411882del", - "genomicLocation": "7,116411867,116411882,GTCTTTAACAAGCTCT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.*963*", - "vepPredictedVariantClassification": "Intron", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265789_41266324del", + "genomicLocation": "3,41265789,41266324,CAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-36_2888-21del", + "hgvsc": "ENST00000349496.5:c.13+217_40del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -3120,40 +3081,86 @@ "therapeuticLevel": null }, { - "variant": "7:g.116412044G>A", - "genomicLocation": "7,116412044,116412044,G,A", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X1010_splice", + "variant": "3:g.41265805_41266404del", + "genomicLocation": "3,41265805,41266404,CTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D963_D1010del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.3028+1G>A", + "hgvsc": "ENST00000349496.5:c.14-212_56del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], - "counts": {}, - "therapeuticLevel": "LEVEL_1" + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null }, { - "variant": "7:g.116411876_116411896del", - "genomicLocation": "7,116411876,116411896,AAGCTCTTTCTTTCTCTCTGT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.X963_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265687_41266331del", + "genomicLocation": "3,41265687,41266331,TTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-27_2888-7del", + "hgvsc": "ENST00000349496.5:c.13+116_14-75del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -3203,23 +3210,23 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "7:g.116411867_116411890del", - "genomicLocation": "7,116411867,116411890,GTCTTTAACAAGCTCTTTCTTTCT,-", - "transcriptId": "ENST00000397752", - "vepPredictedProteinEffect": "p.*963*", - "vepPredictedVariantClassification": "Intron", - "revisedProteinEffect": "p.D963_D1010del", + "variant": "3:g.41265901_41266287del", + "genomicLocation": "3,41265901,41266287,TTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000397752.3:c.2888-36_2888-13del", + "hgvsc": "ENST00000349496.5:c.14-115_153del", "confirmed": false, "references": [ { "pubmedId": "0", - "referenceText": "Confirmed by MSK Clinical Bioinformatics Team (Unpublished)" + "referenceText": "Pending" } ], "counts": { @@ -3269,44 +3276,33 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "PIK3R1", - "transcriptId": "ENST00000521381", - "genomicLocationDescription": "Indels and substitutions flanking exon 11 (e.g. 5:67589663G>A)", - "defaultEffect": "splice", - "comment": "Skipping of exon 11", - "context": "Recurrent in breast and uterine cancer", - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "5:g.67589663G>C", - "genomicLocation": "5,67589663,67589663,G,C", - "transcriptId": "ENST00000521381", - "vepPredictedProteinEffect": "p.X475_splice", + "variant": "3:g.41265743_41266365del", + "genomicLocation": "3,41265743,41266365,CACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D434_E476del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000521381.1:c.1425+1G>C", + "hgvsc": "ENST00000349496.5:c.13+174_242-77del", "confirmed": false, "references": [ { - "pubmedId": "25488983", - "referenceText": "Lucas et al., 2014" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Glioma": 1 + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -3322,12 +3318,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Glioma": 1 + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -3343,12 +3338,11 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Glioma": 1 + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -3357,37 +3351,30 @@ "therapeuticLevel": null }, { - "variant": "5:g.67589663G>A", - "genomicLocation": "5,67589663,67589663,G,A", - "transcriptId": "ENST00000521381", - "vepPredictedProteinEffect": "p.X475_splice", + "variant": "3:g.41265906_41266360del", + "genomicLocation": "3,41265906,41266360,ATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.D434_E476del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000521381.1:c.1425+1G>A", + "hgvsc": "ENST00000349496.5:c.14-110_242-84del", "confirmed": false, "references": [ { - "pubmedId": "25488983", - "referenceText": "Lucas et al., 2014" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 15, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 2, - "Colorectal Cancer": 3, - "Endometrial Cancer": 2, - "Glioma": 2, - "Hepatobiliary Cancer": 1, - "Melanoma": 1, - "Ovarian Cancer": 1, - "Prostate Cancer": 3 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -3403,20 +3390,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 17, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 2, - "Colorectal Cancer": 1, - "Endometrial Cancer": 3, - "Glioma": 3, - "Hepatobiliary Cancer": 1, - "Mature T and NK Neoplasms": 1, - "Melanoma": 1, - "Ovarian Cancer": 1, - "Prostate Cancer": 3, - "Salivary Gland Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -3424,73 +3402,52 @@ "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Esophagogastric Cancer": 1 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 20, - "unknownVariantsCount": 1, - "germlineVariantsCountByCancerType": {}, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 2, - "Colorectal Cancer": 3, - "Endometrial Cancer": 3, - "Glioma": 3, - "Hepatobiliary Cancer": 1, - "Mature T and NK Neoplasms": 1, - "Melanoma": 2, - "Ovarian Cancer": 1, - "Prostate Cancer": 3, - "Salivary Gland Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Esophagogastric Cancer": 1 + "Hepatobiliary Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "FLT3", - "transcriptId": "ENST00000241453", - "genomicLocationDescription": "Indels around tyrosine kinase (e.g. 13:28608214_28608215insTT...)", - "defaultEffect": "splice", - "comment": "Internal Tandem Duplication", - "context": "Recurrent alteration in AML", - "revisedProteinEffects": [ + }, { - "variant": "13:g.28608217_28608218insCCAAACTCTAAATTTTCTCTTGGAAACTCCCATTTGAGATCATATTCATATTCTCTG", - "genomicLocation": "13,28608217,28608218,-,CCAAACTCTAAATTTTCTCTTGGAAACTCCCATTTGAGATCATATTCATATTCTCTG", - "transcriptId": "ENST00000241453", - "vepPredictedProteinEffect": "p.X594_splice", + "variant": "3:g.41265718_41266423del", + "genomicLocation": "3,41265718,41266423,TGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.E598_F612dup", - "revisedVariantClassification": "Splice_Exon_Extension_In_Frame", - "revisedStandardVariantClassification": "In_Frame_Ins", - "hgvsc": "ENST00000241453.7:c.1782_1837+1dup", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+148_242-20del", "confirmed": false, "references": [ { - "pubmedId": "31285539", - "referenceText": "Zhang et al., 2020" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -3509,7 +3466,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Leukemia": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -3529,49 +3486,40 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Leukemia": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "ATM", - "transcriptId": "ENST00000278616", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "missense, splice", - "comment": "Splice leads to exon skip, frameshift and inframe deletion", - "context": "In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer", - "revisedProteinEffects": [ + }, { - "variant": "11:g.108115753G>A", - "genomicLocation": "11,108115753,108115753,G,A", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.G301S", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.C222Qfs*2", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000278616.4:c.901G>A", + "variant": "3:g.41265989_41266510del", + "genomicLocation": "3,41265989,41266510,TAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_L103del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-26_309del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -3590,7 +3538,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Soft Tissue Sarcoma": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -3610,7 +3558,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Soft Tissue Sarcoma": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -3619,73 +3567,50 @@ "therapeuticLevel": null }, { - "variant": "11:g.108127067G>A", - "genomicLocation": "11,108127067,108127067,G,A", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X750_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.I709_K750del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266002_41266229del", + "genomicLocation": "3,41266002,41266229,GTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_Q76del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000278616.4:c.2250G>A", - "confirmed": true, + "hgvsc": "ENST00000349496.5:c.14-15_226del", + "confirmed": false, "references": [ { - "pubmedId": "9887333", - "referenceText": "Sandoval et al., 1999" - }, - { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", - "variantNote": "This heterozygous germline variant ATM c.2250G>A variant does not change the encoded amino acid of the ATM protein (p.Lys750=), however, it falls at the last base pair of exon 14 of ATM. This variant has been identified in <0.01% of Non-Finnish European chromosomes in the genome Aggregation Database (http://gnomad.broadinstitute.org). It has been reported in combination with another pathogenic variant in individuals and families with Ataxia-telangiectasia (PMID: 9463314, 10980530, 9887333, 10330348, 19691550). It has also been reported in the heterozygous state in a BRCA1/2 negative individual undergoing multigene panel testing (PMID:26270727). An experimental study showed that this variant affects splicing and leads to exon skipping of exon 14 (PMID: 9887333). This variant is classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.). Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia.", "counts": { "mskimpact": { - "germlineVariantsCount": 8, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Cancer of Unknown Primary": 2, - "Colorectal Cancer": 1, - "Germ Cell Tumor": 1, - "Non-Small Cell Lung Cancer": 1, - "Pancreatic Cancer": 1, - "Prostate Cancer": 2 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1, - "Endometrial Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 13, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Sarcoma": 1, - "Colorectal Cancer": 1, - "Endometrial Cancer": 1, - "Glioma": 1, - "Hodgkin Lymphoma": 1, - "Mesothelioma": 1, - "Non-Small Cell Lung Cancer": 2, - "Pancreatic Cancer": 3, - "Prostate Cancer": 1, - "Thyroid Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -3700,28 +3625,12 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 8, - "somaticVariantsCount": 15, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Cancer of Unknown Primary": 2, - "Colorectal Cancer": 1, - "Germ Cell Tumor": 1, - "Non-Small Cell Lung Cancer": 1, - "Pancreatic Cancer": 1, - "Prostate Cancer": 2 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Sarcoma": 1, - "Colorectal Cancer": 2, - "Endometrial Cancer": 2, - "Glioma": 1, - "Hodgkin Lymphoma": 1, - "Mesothelioma": 1, - "Non-Small Cell Lung Cancer": 2, - "Pancreatic Cancer": 3, - "Prostate Cancer": 1, - "Thyroid Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -3730,23 +3639,22 @@ "therapeuticLevel": null }, { - "variant": "11:g.108138071T>C", - "genomicLocation": "11,108138071,108138071,T,C", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X880_splice", + "variant": "3:g.41265988_41266211del", + "genomicLocation": "3,41265988,41266211,CTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.A823Vfs*5", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000278616.4:c.2638+2T>C", + "revisedProteinEffect": "p.A5_F70del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-29_208del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -3754,7 +3662,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Esophagogastric Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -3770,10 +3678,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -3792,39 +3702,40 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Esophagogastric Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "11:g.108175400A>C", - "genomicLocation": "11,108175400,108175400,A,C", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X1833_splice", + "variant": "3:g.41265592_41266289del", + "genomicLocation": "3,41265592,41266289,TAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.V1833Ifs*63", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000278616.4:c.5497-2A>C", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+21_241+46del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -3839,10 +3750,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -3857,43 +3770,46 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "11:g.108198370A>C", - "genomicLocation": "11,108198370,108198370,A,C", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X2326_splice", + "variant": "3:g.41265880_41266334del", + "genomicLocation": "3,41265880,41266334,TTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.N2326_K2363del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000278616.4:c.6976-2A>C", + "hgvsc": "ENST00000349496.5:c.14-136_241+91del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": {}, - "totalPatientCount": 70067 + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, @@ -3906,10 +3822,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -3924,41 +3842,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "11:g.108198484_108198522del", - "genomicLocation": "11,108198484,108198522,AGGTAAGATTTTTGGAGCAACCCTTAAGATAGTTACTTA,-", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X2363_splice", + "variant": "3:g.41266015_41266600del", + "genomicLocation": "3,41266015,41266600,AGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.N2326_K2363del", + "revisedProteinEffect": "p.A5_K133del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000278616.4:c.7088_7089+37del", + "hgvsc": "ENST00000349496.5:c.14-1_398del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -3973,10 +3894,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -3991,41 +3914,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "11:g.108214099_108214103del", - "genomicLocation": "11,108214099,108214103,GTGAG,-", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X2806_splice", + "variant": "3:g.41265810_41266364del", + "genomicLocation": "3,41265810,41266364,TCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.V2757_M2806del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000278616.4:c.8418+1_8418+5del", + "hgvsc": "ENST00000349496.5:c.14-204_242-78del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4040,10 +3966,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4058,41 +3986,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "11:g.108236051G>A", - "genomicLocation": "11,108236051,108236051,G,A", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X2996_splice", + "variant": "3:g.41265989_41266253del", + "genomicLocation": "3,41265989,41266253,TAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.S2996Rfs*5", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000278616.4:c.8988-1G>A", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-27_241+10del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4107,10 +4038,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4125,44 +4058,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "11:g.108202764G>A", - "genomicLocation": "11,108202764,108202764,G,A", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X2596_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.L2544_E2596del", + "variant": "3:g.41265648_41266274del", + "genomicLocation": "3,41265648,41266274,CCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000278616.4:c.7788G>A", - "confirmed": true, + "hgvsc": "ENST00000349496.5:c.13+76_241+30del", + "confirmed": false, "references": [ { - "pubmedId": "9792409", - "referenceText": "Broeks et al., 1998" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", - "variantNote": "This heterozygous ATM c.7788G>A p.Glu2596Glu variant is a synonymous variant that occurs at the last nucleotide of exon 52 and does not alter the amino acid at this position. It has been identified in 0.002% of Non-Finnish European chromosomes by the Exome Aggregation Consortium (ExAC: http://exac.broadinstitute.org; dbSNP). This variant has been reported in two homozygous and one compound heterozygous individuals with ataxia-telangiectasia (PMID: 9792409 and 26693373). It has been demonstrated to cause altered splicing, leading to deletion of 53 amino acids in exon 52 (PMID: 9792409). This region includes part of the FAT domain, which has been suggested to be important for proper activity of the protein (PMID: 23532176, 25460276, 10782091, 27229179). In summary, based on the previous reports of this variant in individuals with ataxia-telangiectasia and its impact on the protein, this variant meets our criteria to be classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.) Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia.", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Small Bowel Cancer": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4177,10 +4110,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4194,78 +4129,63 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Small Bowel Cancer": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "11:g.108151895G>A", - "genomicLocation": "11,108151895,108151895,G,A", - "transcriptId": "ENST00000278616", - "vepPredictedProteinEffect": "p.X1192_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.S1135_K1192", + "variant": "3:g.41265739_41266347del", + "genomicLocation": "3,41265739,41266347,AAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000278616.4:c.3576G>A", - "confirmed": true, + "hgvsc": "ENST00000349496.5:c.13+168_242-97del", + "confirmed": false, "references": [ { - "pubmedId": "9887333", - "referenceText": "Sandoval et al., 1999" - }, - { - "pubmedId": "16941484", - "referenceText": "Cavalieri et al., 2006" - }, - { - "pubmedId": "21965147", - "referenceText": "Demuth et al., 2011" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", - "variantNote": "This heterozygous ATM c.3576G>A variant is a synonymous alteration that does not change a Lysine to another amino acid at codon 1192 (p.Lys1192=). This variant occurs in the last nucleotide of an exon and leads to aberrant splicing leading to exon skipping according to in-vitro RNA studies (PMID: 9887333, 16941484, 21965147). This variant has been identified in 4/113572 of Non-Finnish European chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/;), and has been reported in multiple individuals with ataxia telangiectasia in heterozygous (in-trans with another pathogenic ATM variant) or homozygous states (PMID: 30819809, 8845835, 9443866, 9792409, 9887333, 10330348, 12552559, 16941484, 17124347). Furthermore, this variant has been detected in patients with breast, thyroid or ampullary cancers (PMID: 27599564, 30620386, 31300551). In summary, based on the previous reports of this variant in individuals with ATM associated disease and in-vitro functional studies, this variant is classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.) Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia.", "counts": { "mskimpact": { - "germlineVariantsCount": 3, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Colorectal Cancer": 1, - "Non-Small Cell Lung Cancer": 2 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Esophagogastric Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Skin Cancer, Non-Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4279,58 +4199,47 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 3, - "somaticVariantsCount": 2, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Colorectal Cancer": 1, - "Non-Small Cell Lung Cancer": 2 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1, - "Skin Cancer, Non-Melanoma": 1 + "Esophagogastric Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "BRCA1", - "transcriptId": "ENST00000357654", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "missense, splice, intron", - "comment": "Splice leads to frameshift", - "context": null, - "revisedProteinEffects": [ + }, { - "variant": "17:g.41197820C>T", - "genomicLocation": "17,41197820,41197820,C,T", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.X1823_splice", + "variant": "3:g.41265621_41266305del", + "genomicLocation": "3,41265621,41266305,GCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.A1844Dfs*2", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000357654.3:c.5468-1G>A", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+50_241+62del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "germlineVariantsCount": 1, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "germlineVariantsCountByCancerType": { + "Tubular Adenoma of the Colon": 1 + }, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4345,10 +4254,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Tubular Adenoma of the Colon": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4363,47 +4274,43 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "17:g.41228505C>A", - "genomicLocation": "17,41228505,41228505,C,A", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.R1495M", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.A1453Gfs*9", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000357654.3:c.4484G>T", + "variant": "3:g.41265955_41266414del", + "genomicLocation": "3,41265955,41266414,TTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-62_242-31del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 4, - "somaticVariantsCount": 2, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Breast Cancer": 1, - "Glioma": 1, - "Ovarian Cancer": 2 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Ovarian Cancer": 1, - "Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -4419,14 +4326,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 7, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 3, - "Ovarian Cancer": 2, - "Pancreatic Cancer": 1, - "Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -4441,57 +4345,45 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 3, - "somaticVariantsCount": 9, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Breast Cancer": 1, - "Ovarian Cancer": 2 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Glioma": 1, - "Non-Small Cell Lung Cancer": 3, - "Ovarian Cancer": 3, - "Pancreatic Cancer": 1, - "Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "17:g.41258474T>C", - "genomicLocation": "17,41258474,41258474,T,C", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.R71G", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.C64*", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000357654:c.211A>G", + "variant": "3:g.41265625_41266067del", + "genomicLocation": "3,41265625,41266067,TTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_V22del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+56_67del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" - }, - { - "pubmedId": "11385711", - "referenceText": "Vega et al., 2001" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "The BRCA1 c.211A>G variant changes an arginine to glycine at codon 71 (p.R71G). This variant has been identified in 1/249744 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/), and has been reported as a founder mutation in the Spanish population shown to segregate with breast and ovarian cancer in multiple families (PMID: 11385711, 23683081, 27081505, 12014998, 20215541). According to RT-PCR analysis, this variants leads to an aberrantly spliced mRNA creating a premature stop codon (p.Cys64*) (PMID: 11385711, 19123044, 20215541, 21735045). Heterozygous truncating variants in BRCA1 are known to be pathogenic. Note: this variant is also known as 330A>G in the literature. The sequence analysis indicated that 22 base pairs of exon 4 were deleted, creating with the first bases of exon 5, a termination codon at position 64", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Ovarian Cancer": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Hepatobiliary Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4506,12 +4398,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Ovarian Cancer": 1, - "Pancreatic Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -4526,47 +4417,45 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 2, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Ovarian Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Ovarian Cancer": 1, - "Pancreatic Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "17:g.41258472C>T", - "genomicLocation": "17,41258472,41258472,C,T", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.X71_splice", + "variant": "3:g.41265977_41266368del", + "genomicLocation": "3,41265977,41266368,TTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCAC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.C64*", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000357654:c.212+1G>A", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-37_242-74del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "Deletion of 22 bp at the end of exon 4", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4585,7 +4474,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -4605,41 +4494,40 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "17:g.41256985T>C", - "genomicLocation": "17,41256985,41256985,T,C", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.*71*", - "vepPredictedVariantClassification": "Intron", - "revisedProteinEffect": "p.R71Sfs*20", - "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Ins", - "hgvsc": "ENST00000357654:c.213-12A>G", + "variant": "3:g.41265922_41266247del", + "genomicLocation": "3,41265922,41266247,AAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-94_241+4del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "Insertion of 11 bp of intro 4 at the beginning of exon 5", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Breast Cancer": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4654,10 +4542,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4671,13 +4561,13 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Breast Cancer": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -4685,53 +4575,31 @@ "therapeuticLevel": null }, { - "variant": "17:g.41234420C>A", - "genomicLocation": "7,116412044,116412044,G,A", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.X1453_splice", - "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.R1397Yfs*2", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000357654:c.4357+1G>T", - "confirmed": false, - "references": [ - { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" - } - ], - "variantNote": "Skipping of exon 12", - "otherVariation": "Deletion of the first three bases of exon 14 (r.4358_4360del), leading to an in-frame deletion of the amino acid alanine at codon 1,453 (p.Ala1453del)", - "counts": {}, - "therapeuticLevel": "LEVEL_1" - }, - { - "variant": "17:g.41234420del", - "genomicLocation": "17,41234420,41234420,C,-", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.X1453_splice", + "variant": "3:g.41265888_41266277del", + "genomicLocation": "3,41265888,41266277,TTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.A1453Qfs*3", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000357654:c.4357+1delG", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-129_241+33del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "Deletion of a guanine at the last base of exon 12 (r.4357del) because of the use of a cryptic donor splice site created by the DNA mutation", - "otherVariation": "Can also be a a skipping of exon 13, although in the case of c.4357+1delG this aberrant band is observed in a lower proportion; this frameshift deletion is predicted to generate a premature stop codon (p.Arg1397TyrfsX2)", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4746,10 +4614,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4764,41 +4634,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "17:g.41228504C>A", - "genomicLocation": "17,41228504,41228504,C,A", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.X1495_splice", + "variant": "3:g.41265782_41266409del", + "genomicLocation": "3,41265782,41266409,CTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.A1453Gfs*10", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000357654:c.4484+1G>T", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+213_242-33del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "This mutation arises in the invariant guanine in the consensus sequence of the 5' donor splice site of exon 13. cDNA analysis showed that this mutation abolishes the natural 5_ splice site of exon 13, causing complete deletion of this exon (r.4358_4484del)", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4813,10 +4686,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4831,42 +4706,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "17:g.41219622T>C", - "genomicLocation": "17,41219622,41219622,T,C", - "transcriptId": "ENST00000357654", - "vepPredictedProteinEffect": "p.*1692*", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D1692Gfs*15", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Ins", - "hgvsc": "ENST00000357654:c.5074+3A>G", + "variant": "3:g.41265591_41266253del", + "genomicLocation": "3,41265591,41266253,TTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+22_241+12del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "The BRCA1 c.5074+3A>G variant was identified in a woman with bilateral breast cancer; her mother, who was diagnosed with breast cancer at age 53 and with colorectal cancer at age 68, carried the same variant. RNA analysis of this variant shows an insertion of the first 153 bp of intron 16 (r.5074_5075ins5074+1_5074+153). the pathogenicity of this mutation may derive from the splicing anomalies detected and is supported by the co-segregation with breast cancer observed in this family.", - "otherVariation": "Can also be a skipping of exon 17 (r.4987_5074del), which is predicted to lead to the truncated proteins p.Val1665SerfsX8", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4881,10 +4758,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -4899,51 +4778,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "BRCA2", - "transcriptId": "ENST00000380152", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "splice, intron", - "comment": "Splice leads to frameshift", - "context": null, - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "13:g.32900634A>G", - "genomicLocation": "13,32900634,32900634,A,G", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.X173_splice", + "variant": "3:g.41266007_41266408del", + "genomicLocation": "3,41266007,41266408,GTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.G173Sfs*17", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000380152.3:c.517-2A>G", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-10_242-37del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -4958,12 +4830,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Melanoma": 1, - "Non-Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -4979,44 +4850,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Melanoma": 1, - "Non-Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "13:g.32931878G>A", - "genomicLocation": "13,32931878,32931878,G,A", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.X2540_splice", + "variant": "3:g.41265823_41266422del", + "genomicLocation": "3,41265823,41266422,GTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.L2540Qfs*10", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000380152.3:c.7618-1G>A", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-192_242-21del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -5031,14 +4902,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 3, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Ovarian Cancer": 1, - "Pancreatic Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -5053,72 +4920,62 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 3, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Ovarian Cancer": 1, - "Pancreatic Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "13:g.32954050G>A", - "genomicLocation": "13,32954050,32954050,G,A", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.X3039_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.V2985Gfs*3", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000380152.3:c.9117G>A", + "variant": "3:g.41265947_41266244del", + "genomicLocation": "3,41265947,41266244,CAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-70_241del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 2, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Prostate Cancer": 2 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Skin Cancer, Non-Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 4, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Breast Cancer": 2, - "Colorectal Cancer": 1, - "Ovarian Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -5132,49 +4989,45 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 2, - "somaticVariantsCount": 6, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Prostate Cancer": 2 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Breast Cancer": 2, - "Colorectal Cancer": 1, - "Ovarian Cancer": 1, - "Skin Cancer, Non-Melanoma": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "13:g.32919384T>G", - "genomicLocation": "13,32919384,32919384,T,G", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.*2313*", - "vepPredictedVariantClassification": "Intron", - "revisedProteinEffect": "p.G2313Gfs*9", - "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Ins", - "hgvsc": "ENST00000380152.3:c.6937+594T>G", + "variant": "3:g.41265921_41266361del", + "genomicLocation": "3,41265921,41266361,TAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-96_242-84del", "confirmed": false, "references": [ { - "pubmedId": "22753590", - "referenceText": "Anczuków et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Hepatobiliary Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -5207,10 +5060,12 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Hepatobiliary Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -5218,33 +5073,28 @@ "therapeuticLevel": null }, { - "variant": "13:g.32900635G>A", - "genomicLocation": "13,32900635,32900635,G,A", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.X173_splice", + "variant": "3:g.41265792_41266371del", + "genomicLocation": "3,41265792,41266371,TACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.G173Sfs*19", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000380152.3:c.517-1G>A", - "confirmed": false, - "references": [ + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-218_242-67del", + "confirmed": false, + "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "Leads to a skipping of exon 7 (r.517_631del)", - "otherVariation": "Activate a cryptic donor splice site that leads to the skipping of most of exon 6 and all of exon 7 (r.478_631del). This transcript is predicted to lead to a truncated protein (p.Val160SerfsX19)", "counts": { "mskimpact": { - "germlineVariantsCount": 2, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Pancreatic Cancer": 1, - "Prostate Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -5277,38 +5127,34 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 2, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Pancreatic Cancer": 1, - "Prostate Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "13:g.32907378A>G", - "genomicLocation": "13,32907378,32907378,A,G", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.N588S", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.N588_G637delinsS", - "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "variant": "3:g.41265957_41266436del", + "genomicLocation": "3,41265957,41266436,TTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000380152.3:c.1763A>G", + "hgvsc": "ENST00000349496.5:c.14-56_242-5del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "Identified in a woman diagnosed with breast cancer at age 31. This variant creates a new cryptic donor site, which leads to an alternative transcript consisting of an in-frame deletion of 147 nucleotides (r.1763_1909del) that, in turn, produces an in-frame deletion of 49 amino acids with the insertion of a serine (p.Asn588_Gly637delinsSer)", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -5359,32 +5205,29 @@ "therapeuticLevel": null }, { - "variant": "13:g.32944538G>A", - "genomicLocation": "13,32944538,32944538,G,A", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.X2778_splice", + "variant": "3:g.41265946_41266408del", + "genomicLocation": "3,41265946,41266408,ACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.I2778Yfs*15", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000380152.3:c.8332-1G>A", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-69_242-35del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "This mutation arises in the invariant dinucleotide in the consensus sequence of the 3_ acceptor splice site of exon 19. cDNA analysis of the mutation showed that this mutation abolishes the natural 3_ splice site of exon 19 and leads to the activation of a cryptic splice site 14 bp downstream. Consequently, the mutated transcript shows a 14-bp deletion at the beginning of exon 19 (r.8332_8345del).", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Esophagogastric Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -5399,13 +5242,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Esophagogastric Cancer": 1, - "Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -5420,37 +5260,33 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Esophagogastric Cancer": 1, - "Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "13:g.32953872T>G", - "genomicLocation": "13,32953872,32953872,T,G", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.*2985*", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.V2985Afs*8", - "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Ins", - "hgvsc": "ENST00000380152.3:c.8954-15T>G", + "variant": "3:g.41265991_41266603del", + "genomicLocation": "3,41265991,41266603,ATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAAC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_H134del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-22_404del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "It creates a new cryptic donor site that leads to an alternative transcript with an insertion of the last 14 nucleotides of intron 22 (r.8953_8954ins8954-14_8954-1), generating a truncated protein (p.Val2985AlafsX8). Segregation analysis showed that the two sisters with breast cancer (diagnosed at 29 and 40 years old, respectively) are carriers of this variant, which was inherited from their unaffected father whose history is non-informative of HBOCS.", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -5498,35 +5334,31 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "13:g.32953882A>G", - "genomicLocation": "13,32953882,32953882,A,G", - "transcriptId": "ENST00000380152", - "vepPredictedProteinEffect": "p.X2985_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.V2985Dfs*34", - "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Ins", - "hgvsc": "ENST00000380152.3:c.8954-5A>G", + "variant": "3:g.41265757_41266254del", + "genomicLocation": "3,41265757,41266254,TAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+187_241+12del", "confirmed": false, "references": [ { - "pubmedId": "21735045", - "referenceText": "Menéndez et al., 2012" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "It creates a novel cryptic donor site that leads to an alternative transcript with an insertion of the last four nucleotides of intron 22 (r.8953_8954ins8954-4_8954-1), generating a truncated protein (p.Val2985AspfsX34). The variant was observed in a young female patient with metachronic bilateral cancer diagnosed at 36 and 42 years who has no relative affected by tumors associated with HBOCS.", "counts": { "mskimpact": { - "germlineVariantsCount": 2, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Endometrial Cancer": 1, - "Prostate Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -5559,57 +5391,40 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 2, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Endometrial Cancer": 1, - "Prostate Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "BRIP1", - "transcriptId": "ENST00000259008", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "splice", - "comment": "Skip exon 5", - "context": "Reported in individuals with breast and ovarian cancers", - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "17:g.59926490C>T", - "genomicLocation": "17,59926490,59926490,C,T", - "transcriptId": "ENST00000259008", - "vepPredictedProteinEffect": "p.X169_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.D127Dfs*1", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000259008.2:c.507G>A", - "confirmed": true, + "variant": "3:g.41265954_41266315del", + "genomicLocation": "3,41265954,41266315,TTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-63_241+71del", + "confirmed": false, "references": [ { - "pubmedId": "29368626", - "referenceText": "Weber-Lassalle et al., 2018" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", - "variantNote": "This silent sequence change affects codon 169 of the BRIP1 mRNA and does not change the encoded amino acid sequence (p.Gln169=). This variant falls at the last nucleotide of BRIP1 exon 5. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD), and has been reported in the literature in individuals with breast and ovarian cancers (PMID: 29368626). An experimental study using patient RNA showed that this variant led to skipping of exon 5 and a prematurely truncated protein product (PMID: 29368626). In summary, although additional studies are required to fully establish its clinical significance, this BRIp1 c.507G>A p.Gln169= variant is classified as likely pathogenic. Heterozygous pathogenic variants in BRIP1 have been associated with an increased risk of ovarian cancer (PMID: 26315354, 2196457) and may increase the risk of breast cancer (PMID: 17033622). Biallelic mutations in BRIP1 have been associated with Fanconi Anemia, an autosomal recessive condition characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. If a BRIP1 mutation carrier's partner is heterozygous for a pathogenic BRIP1 mutation, there is a 25% risk that each child would be affected by Fanconi Anemia.", "counts": { "mskimpact": { - "germlineVariantsCount": 1, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Endometrial Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -5625,12 +5440,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -5644,39 +5457,34 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 1, + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Endometrial Cancer": 1 - }, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "17:g.59938807C>T", - "genomicLocation": "17,59938807,59938807,C,T", - "transcriptId": "ENST00000259008", - "vepPredictedProteinEffect": "p.X31_splice", + "variant": "3:g.41265647_41266373del", + "genomicLocation": "3,41265647,41266373,CCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.M1_S31del", - "revisedVariantClassification": "Splice_Exon_Skip_Non_Start", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000259008.2:c.93+1G>A", + "hgvsc": "ENST00000349496.5:c.13+77_242-70del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -5724,51 +5532,32 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "CDH1", - "transcriptId": "ENST00000261769", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "missense, splice", - "comment": "Splice leads to frameshift(exon 11) and nonsense(exon 10)", - "context": null, - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "16:g.68849663G>A", - "genomicLocation": "16,68849663,68849663,G,A", - "transcriptId": "ENST00000261769", - "vepPredictedProteinEffect": "p.X522_splice", + "variant": "3:g.41265747_41266399del", + "genomicLocation": "3,41265747,41266399,AGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.T523*", - "revisedVariantClassification": "Splice_Exon_Extension_Nonsense", - "revisedStandardVariantClassification": "Nonsense_Mutation", - "hgvsc": "ENST00000261769.5:c.1565+1G>A", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+176_242-45del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 12, + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, - "somaticVariantsCountByCancerType": { - "Breast Cancer": 3, - "Cancer of Unknown Primary": 1, - "Colorectal Cancer": 4, - "Esophagogastric Cancer": 3, - "Glioma": 1 - }, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -5783,97 +5572,67 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 20, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Breast Cancer": 6, - "Cancer of Unknown Primary": 1, - "Colorectal Cancer": 5, - "Endometrial Cancer": 1, - "Esophagogastric Cancer": 6, - "Glioma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 2, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Breast Cancer": 2 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 21, - "unknownVariantsCount": 2, - "germlineVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, - "somaticVariantsCountByCancerType": { - "Breast Cancer": 6, - "Cancer of Unknown Primary": 1, - "Colorectal Cancer": 5, - "Endometrial Cancer": 1, - "Esophagogastric Cancer": 7, - "Glioma": 1 - }, - "unknownVariantsCountByCancerType": { - "Breast Cancer": 2 - }, + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null }, { - "variant": "16:g.68845762G>A", - "genomicLocation": "16,68845762,68845762,G,A", - "transcriptId": "ENST00000261769", - "vepPredictedProteinEffect": "p.X336_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.S337Vfs*14", - "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Ins", - "hgvsc": "ENST00000261769.5:c.1008G>A", + "variant": "3:g.41265879_41266283del", + "genomicLocation": "3,41265879,41266283,ATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-136_241+41del", "confirmed": false, "references": [ { - "pubmedId": "8127895", - "referenceText": "Oda et al., 1994" - }, - { - "pubmedId": "18427545", - "referenceText": "Karam et al., 2008" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "The heterozygous germline variant, CDH1 c.1008G>A (p.Glu336=) is located at the last nucleotide of exon 7 of the CDH1 gene. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD) and has been reported in an individual affected with diffuse gastric cancer (PMID: 27730413). Experimental studies and analysis of RNA demonstrated that this variant leads to aberrant splicing (PMID: 8127895, 18427545). Additionally, a different variant at this position (c.1008G>T) has been reported in a family affected with hereditary diffuse gastric cancer (PMID: 9537325, 19725995). In summary, although additional studies are required to fully establish its clinical significance, this c.1008G>A variant is classified as likely pathogenic.", - "otherVariation": "Can also be 25, 42, 150 bp intron 7 insertion, and whole intron 7 insertions", "counts": { "mskimpact": { - "germlineVariantsCount": 1, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Esophagogastric Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, @@ -5889,59 +5648,48 @@ "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Breast Cancer": 1 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 1, - "unknownVariantsCount": 1, - "germlineVariantsCountByCancerType": { - "Esophagogastric Cancer": 1 - }, - "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Breast Cancer": 1 - }, + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null }, { - "variant": "16:g.68853328G>A", - "genomicLocation": "16,68853328,68853328,G,A", - "transcriptId": "ENST00000261769", - "vepPredictedProteinEffect": "p.G571S", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.Y523Ffs*15", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000261769.5:c.1711G>A", + "variant": "3:g.41265913_41266289del", + "genomicLocation": "3,41265913,41266289,TTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.14-101_241+48del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -5956,13 +5704,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "B-Lymphoblastic Leukemia/Lymphoma": 1, - "Colorectal Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -5977,66 +5722,40 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "B-Lymphoblastic Leukemia/Lymphoma": 1, - "Colorectal Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "CHEK2", - "transcriptId": "ENST00000328354", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "splice", - "comment": "Splice leads to frameshift", - "context": null, - "revisedProteinEffects": [ + }, { - "variant": "22:g.29121230C>T", - "genomicLocation": "22,29121230,29121230,C,T", - "transcriptId": "ENST00000328354", - "vepPredictedProteinEffect": "p.X148_splice", + "variant": "3:g.41265761_41266271del", + "genomicLocation": "3,41265761,41266271,CTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.E149Ifs*5", - "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Ins", - "hgvsc": "ENST00000328354.6:c.444+1G>A", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.13+192_241+30del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 13, - "somaticVariantsCount": 1, + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Breast Cancer": 2, - "Colorectal Cancer": 2, - "Glioma": 1, - "Melanoma": 2, - "Non-Small Cell Lung Cancer": 1, - "Pancreatic Cancer": 1, - "Peripheral Nervous System": 1, - "Prostate Cancer": 2 - }, - "somaticVariantsCountByCancerType": { - "Mesothelioma": 1 - }, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -6051,14 +5770,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 4, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1, - "Glioma": 2, - "Mesothelioma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -6072,59 +5787,34 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 10, - "somaticVariantsCount": 7, + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Breast Cancer": 2, - "Colorectal Cancer": 2, - "Melanoma": 1, - "Non-Small Cell Lung Cancer": 1, - "Pancreatic Cancer": 1, - "Peripheral Nervous System": 1, - "Prostate Cancer": 2 - }, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Colorectal Cancer": 1, - "Glioma": 3, - "Melanoma": 1, - "Mesothelioma": 1 - }, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "PALB2", - "transcriptId": "ENST00000261584", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "splice", - "comment": "Splice leads to exon 9 or exon 6 skipping", - "context": null, - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "16:g.23634452C>G", - "genomicLocation": "16,23634452,23634452,C,G", - "transcriptId": "ENST00000261584", - "vepPredictedProteinEffect": "p.X945_splice", + "variant": "3:g.41265965_41266375del", + "genomicLocation": "3,41265965,41266375,ATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.A946_G999del", + "revisedProteinEffect": "p.A5_D81del", "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000261584.4:c.2835-1G>C", + "hgvsc": "ENST00000349496.5:c.14-49_242-67del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -6172,34 +5862,31 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "16:g.23640597C>A", - "genomicLocation": "16,23640597,23640597,C,A", - "transcriptId": "ENST00000261584", - "vepPredictedProteinEffect": "p.X839_splice", + "variant": "3:g.41265859_41266211del", + "genomicLocation": "3,41265859,41266211,CTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X5_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.T839_K862del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedProteinEffect": "p.A5_F70del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000261584.4:c.2515-1G>T", + "hgvsc": "ENST00000349496.5:c.14-158_208del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 1, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Pancreatic Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -6232,56 +5919,43 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Pancreatic Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "RAD51D", - "transcriptId": "ENST00000590016", - "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", - "defaultEffect": "splice", - "comment": "Splice leads to frameshift exon truncation", - "context": null, - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "17:g.33428057T>A", - "genomicLocation": "17,33428057,33428057,T,A", - "transcriptId": "ENST00000590016", - "vepPredictedProteinEffect": "p.X302_splice", + "variant": "3:g.41266018_41266622del", + "genomicLocation": "3,41266018,41266622,TGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X6_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.P322Vfs*5", - "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000590016.1:c.964-2A>T", + "revisedProteinEffect": "p.A5_I140del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.16_420del", "confirmed": false, "references": [ { - "pubmedId": "31843900", - "referenceText": "Casadei et al., 2019" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Endometrial Cancer": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Hepatobiliary Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -6300,7 +5974,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -6315,91 +5989,64 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, + "germlineVariantsCount": 0, "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Endometrial Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "MLH1", - "transcriptId": "ENST00000231790", - "genomicLocationDescription": "Last nucleotide of exon 15;Alterations on the ESE motifs cause deletion of exons", - "defaultEffect": "splice", - "comment": "Skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation; Alters number of ESEs affecting transcription", - "context": "In Lynch syndrome colorectal cancer and multiple cancer types", - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "3:g.37083822G>A", - "genomicLocation": "3,37083822,37083822,G,A", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.X577_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.S556Rfs*13", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000231790.2:c.1731G>A", - "confirmed": true, + "variant": "3:g.41266017_41266367del", + "genomicLocation": "3,41266017,41266367,CTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X6_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A5_D81del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.16_242-76del", + "confirmed": false, "references": [ { - "pubmedId": "16341550", - "referenceText": "Pagenstecher et al., 2006" - }, - { - "pubmedId": "18561205", - "referenceText": "Tournier et al., 2008" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", - "variantNote": "The heterozygous germline variant, MLH1 c.1731G>A (p.Ser577Ser), results in a silent mutation and occurs at the last nucleotide of exon 15. This variant is absent from the major population databases (1000G, ESP and gnomAD). It is a well known pathogenic variant that has been reported in several individuals and families with Lynch syndrome (PMID: 16341550, 15849733, 20223024, 26300997, 14635101, 16216036, 16395668, 19669161). Experimental studies using mRNA isolated from patients blood as well as a reporter minigene assay showed that this variant results in the skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation (PMID: 16341550, 18561205, 16451135). In summary, based on the previous reports of this variant in individuals with MLH1 associated cancers and its truncating effect on the protein, this variant meets our criteria to be classified as pathogenic. Lynch syndrome is an autosomal dominant condition that confers an increased risk for colorectal cancer and endometrial cancers as well as other cancers. There is a 50% chance that each child would inherit this variant from a carrier parent.", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Pancreatic Cancer": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 6, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 5, - "Endometrial Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 7, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 4, - "Endometrial Cancer": 1, - "Glioma": 2 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -6414,41 +6061,36 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 13, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Pancreatic Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 9, - "Endometrial Cancer": 2, - "Glioma": 2 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "3:g.37059048C>T", - "genomicLocation": "3,37059048,37059048,C,T", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.A281V", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.H264Lfs*2", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000231790.2:c.842C>T", + "variant": "3:g.41266028_41266605del", + "genomicLocation": "3,41266028,41266605,GAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X9_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.M8_H134del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.26_403del", "confirmed": false, "references": [ { - "pubmedId": "16995940", - "referenceText": "Lastella et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "Alterations on the ESE motifs cause deletion of exons, affects splicing across multiple cancer types", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -6456,7 +6098,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Appendiceal Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -6476,7 +6118,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Appendiceal Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -6484,55 +6126,52 @@ "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Head and Neck Cancer": 1 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { "germlineVariantsCount": 0, "somaticVariantsCount": 1, - "unknownVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Appendiceal Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Head and Neck Cancer": 1 + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null }, { - "variant": "3:g.37090087G>C", - "genomicLocation": "3,37090087,37090087,G,C", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.R659P", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.E633_E663del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266024_41266592del", + "genomicLocation": "3,41266024,41266592,GATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X9_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.L7_Q130del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000231790.2:c.1976G>C", + "hgvsc": "ENST00000349496.5:c.25_393del", "confirmed": false, "references": [ { - "pubmedId": "16995940", - "referenceText": "Lastella et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "Alterations on the ESE motifs cause deletion of exons, affects splicing across multiple cancer types", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -6547,10 +6186,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -6565,52 +6206,53 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "3:g.37050394C>T", - "genomicLocation": "3,37050394,37050394,C,T", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.X181_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.G181Gfs*20", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000231790.2:c.543C>T", + "variant": "3:g.41266032_41266609del", + "genomicLocation": "3,41266032,41266609,TGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X10_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.L10_V136del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.30_407del", "confirmed": false, "references": [ { - "pubmedId": "28334867", - "referenceText": "Yamaguchi et al., 2017" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, @@ -6644,33 +6286,35 @@ "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "3:g.37053309A>G", - "genomicLocation": "3,37053309,37053309,A,G", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.X182_splice", + "variant": "3:g.41266031_41266617del", + "genomicLocation": "3,41266031,41266617,TTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAAC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X11_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.R84Sfs*5", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000231790.2:c.546-2A>G", + "revisedProteinEffect": "p.E9_N138del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.31_417del", "confirmed": false, "references": [ { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Ampullary Cancer": 1, + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -6685,68 +6329,63 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Ampullary Cancer": 1, + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Endometrial Cancer": 1 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, - "unknownVariantsCount": 1, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Endometrial Cancer": 1 + "somaticVariantsCountByCancerType": { + "Ampullary Cancer": 1, + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" + "therapeuticLevel": null }, { - "variant": "3:g.37053590G>T", - "genomicLocation": "3,37053590,37053590,G,T", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.R226L", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.Q197Rfs*7", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000231790.2:c.677G>T", + "variant": "3:g.41266037_41266620del", + "genomicLocation": "3,41266037,41266620,ATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X12_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.D11_L139del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.34_241+47del", "confirmed": false, "references": [ { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 1, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -6779,12 +6418,10 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, + "germlineVariantsCount": 0, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Colorectal Cancer": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -6793,33 +6430,30 @@ "therapeuticLevel": null }, { - "variant": "3:g.37059089A>C", - "genomicLocation": "3,37059089,37059089,A,C", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.S295R", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.H264Lfs*1", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000231790.2:c.883A>C", + "variant": "3:g.41266035_41266624del", + "genomicLocation": "3,41266035,41266624,ACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X12_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.D11_N141del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.34_423del", "confirmed": false, "references": [ { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 0, + "germlineVariantsCount": 1, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": {}, + "germlineVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -6835,10 +6469,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -6853,10 +6489,12 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -6864,37 +6502,31 @@ "therapeuticLevel": null }, { - "variant": "3:g.37067499G>C", - "genomicLocation": "3,37067499,37067499,G,C", - "transcriptId": "ENST00000231790", - "vepPredictedProteinEffect": "p.X470_splice", + "variant": "3:g.41266041_41266672del", + "genomicLocation": "3,41266041,41266672,CCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCCTGAACTGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X13_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.T347Kfs*7", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000231790.2:c.1409+1G>C", + "revisedProteinEffect": "p.A13_T157del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.39_470del", "confirmed": false, "references": [ { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 1, + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Renal Cell Carcinoma": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1 + "Colorectal Cancer": 1, + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -6910,11 +6542,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1 + "Colorectal Cancer": 1, + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -6929,56 +6562,45 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 1, + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Renal Cell Carcinoma": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1 + "Colorectal Cancer": 1, + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "EGFR", - "transcriptId": "ENST00000275493", - "genomicLocationDescription": "5 bases upstream from the 5' end of exon 20 (7:g.55248980_55248981insTCCAGGAAGCCT)", - "defaultEffect": "splice", - "comment": "Inset a repeated sequence from 55248980-55248992", - "context": "Recurrent in lung cancer, can be linked to Level 1 TKIs", - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "7:g.55248980_55248981insTCCAGGAAGCCT", - "genomicLocation": "7,55248980,55248981,-,TCCAGGAAGCCT", - "transcriptId": "ENST00000275493", - "vepPredictedProteinEffect": "p.X762_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.A763_Y764insFQEA", - "revisedVariantClassification": "Splice_Exon_Extension_In_Frame", - "revisedStandardVariantClassification": "In_Frame_Ins", - "hgvsc": "ENST00000275493.2:c.2284-5_2290dup", - "confirmed": true, + "variant": "3:g.41266038_41266669del", + "genomicLocation": "3,41266038,41266669,TGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCCTGAAC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X13_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.M12_L156del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.37_468del", + "confirmed": false, "references": [ { - "pubmedId": "31715539", - "referenceText": "Sousa et al., 2020" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 9, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 9 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -6994,12 +6616,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 13, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 13 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -7014,46 +6634,35 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 16, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 16 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, - "therapeuticLevel": "LEVEL_1" - } - ] - }, - { - "hugoGeneSymbol": "TP53", - "transcriptId": "ENST00000269305", - "genomicLocationDescription": "c.375+5G mutations flanking exon 4", - "defaultEffect": "splice", - "comment": "Splice leads to whole exon 4 skipping inframe deletion or partial exon 4 skipping frameshift", - "context": "Recurrent in many cancer types and results in P53 protein loss of function", - "revisedProteinEffects": [ + "therapeuticLevel": null + }, { - "variant": "17:g.7579307C>A", - "genomicLocation": "17,7579307,7579307,C,A", - "transcriptId": "ENST00000269305", - "vepPredictedProteinEffect": "p.X125_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.S33_T125del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266041_41266373del", + "genomicLocation": "3,41266041,41266373,CCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X14_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A13_D81del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000269305.4:c.375+5G>T", - "confirmed": true, + "hgvsc": "ENST00000349496.5:c.38_241+51del", + "confirmed": false, "references": [ { - "pubmedId": "34505757", - "referenceText": "Chui et al., 2021" + "pubmedId": "0", + "referenceText": "Pending" } ], - "otherVariation": "Partial exon 4 skip, p.G59Vfs*23, Splice_Exon_Shortening_Frame_Shift", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -7066,47 +6675,19 @@ }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 49, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Anal Cancer": 1, - "Bladder Cancer": 2, - "Breast Cancer": 3, - "Cancer of Unknown Primary": 3, - "Colorectal Cancer": 6, - "Endometrial Cancer": 2, - "Esophagogastric Cancer": 1, - "Glioma": 3, - "Non-Small Cell Lung Cancer": 10, - "Ovarian Cancer": 6, - "Pancreatic Cancer": 6, - "Peritoneal Cancer, NOS": 1, - "Sellar Tumor": 1, - "Small Cell Lung Cancer": 2, - "Soft Tissue Sarcoma": 2 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 29, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Breast Cancer": 3, - "Cancer of Unknown Primary": 3, - "Colorectal Cancer": 6, - "Esophagogastric Cancer": 4, - "Glioma": 2, - "Head and Neck Cancer": 1, - "Non-Small Cell Lung Cancer": 5, - "Pancreatic Cancer": 1, - "Prostate Cancer": 1, - "Skin Cancer, Non-Melanoma": 2, - "Soft Tissue Sarcoma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -7121,29 +6702,10 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 78, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Anal Cancer": 1, - "Bladder Cancer": 2, - "Breast Cancer": 6, - "Cancer of Unknown Primary": 6, - "Colorectal Cancer": 12, - "Endometrial Cancer": 2, - "Esophagogastric Cancer": 5, - "Glioma": 5, - "Head and Neck Cancer": 1, - "Non-Small Cell Lung Cancer": 15, - "Ovarian Cancer": 6, - "Pancreatic Cancer": 7, - "Peritoneal Cancer, NOS": 1, - "Prostate Cancer": 1, - "Sellar Tumor": 1, - "Skin Cancer, Non-Melanoma": 2, - "Small Cell Lung Cancer": 2, - "Soft Tissue Sarcoma": 3 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -7151,88 +6713,50 @@ "therapeuticLevel": null }, { - "variant": "17:g.7579312C>A", - "genomicLocation": "17,7579312,7579312,C,A", - "transcriptId": "ENST00000269305", - "vepPredictedProteinEffect": "p.X125_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.S33_T125del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266043_41266623del", + "genomicLocation": "3,41266043,41266623,ATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X14_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A13_I140del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000269305.4:c.375G>T", - "confirmed": true, + "hgvsc": "ENST00000349496.5:c.41_421del", + "confirmed": false, "references": [ { - "pubmedId": "11420676", - "referenceText": "Varley et al., 2001" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", - "variantNote": "The heterozygous germline variant, TP53 c.375G>T (Thr125=), is located at the last nucleotide of exon 4 of the TP53 gene. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD). It has been reported in a family with Li Fraumeni syndrome (PMID: 11420676). In vitro studies and analysis of RNA from patient cells demonstrated that this variant leads to aberrant splicing (PMID: 11420676, 25730903). Two other variants at this position (c.375G>A and c.375G>C) have been reported in individuals and families with Li Fraumeni syndrome (PMID: 9242456, 10864200, 11420676, 24382691, 31105275). In summary, although additional studies are required to fully establish its clinical significance, based on its previous report in an individual with Li Fraumeni syndrome and its demonstrated impact on splicing, this c.375G>T (p.?) variant is classified as likely pathogenic. Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome associated with an increased risk of tumors including soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias (http://www.ncbi.nlm.nih.gov/books/NBK1311/).", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 2 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 124, - "unknownVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 1, - "Bladder Cancer": 4, - "Bone Cancer": 1, - "Breast Cancer": 3, - "Cancer of Unknown Primary": 5, - "Colorectal Cancer": 6, - "Endometrial Cancer": 1, - "Esophagogastric Cancer": 1, - "Head and Neck Cancer": 5, - "Hepatobiliary Cancer": 1, - "Non-Small Cell Lung Cancer": 78, - "Pancreatic Cancer": 4, - "Prostate Cancer": 1, - "Skin Cancer, Non-Melanoma": 2, - "Small Cell Lung Cancer": 9, - "Soft Tissue Sarcoma": 1, - "Uterine Sarcoma": 1 - }, - "unknownVariantsCountByCancerType": { - "Hepatobiliary Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 110, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 1, - "Ampullary Cancer": 1, - "Bladder Cancer": 2, - "Breast Cancer": 2, - "Cancer of Unknown Primary": 12, - "Colorectal Cancer": 1, - "Esophagogastric Cancer": 2, - "Gastrointestinal Neuroendocrine Tumor": 1, - "Glioma": 3, - "Head and Neck Cancer": 3, - "Hepatobiliary Cancer": 2, - "Melanoma": 2, - "Non-Small Cell Lung Cancer": 69, - "Ovarian Cancer": 1, - "Prostate Cancer": 2, - "Renal Cell Carcinoma": 1, - "Skin Cancer, Non-Melanoma": 1, - "Small Bowel Cancer": 1, - "Small Cell Lung Cancer": 3 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -7240,101 +6764,52 @@ "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 25, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 1, - "Bladder Cancer": 2, - "Endometrial Cancer": 2, - "Glioma": 1, - "Head and Neck Cancer": 3, - "Hepatobiliary Cancer": 1, - "Non-Small Cell Lung Cancer": 14, - "Ovarian Epithelial Tumor": 1 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 234, - "unknownVariantsCount": 26, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 2, - "Ampullary Cancer": 1, - "Bladder Cancer": 6, - "Bone Cancer": 1, - "Breast Cancer": 5, - "Cancer of Unknown Primary": 17, - "Colorectal Cancer": 7, - "Endometrial Cancer": 1, - "Esophagogastric Cancer": 3, - "Gastrointestinal Neuroendocrine Tumor": 1, - "Glioma": 3, - "Head and Neck Cancer": 8, - "Hepatobiliary Cancer": 3, - "Melanoma": 2, - "Non-Small Cell Lung Cancer": 147, - "Ovarian Cancer": 1, - "Pancreatic Cancer": 4, - "Prostate Cancer": 3, - "Renal Cell Carcinoma": 1, - "Skin Cancer, Non-Melanoma": 3, - "Small Bowel Cancer": 1, - "Small Cell Lung Cancer": 12, - "Soft Tissue Sarcoma": 1, - "Uterine Sarcoma": 1 - }, - "unknownVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 1, - "Bladder Cancer": 2, - "Endometrial Cancer": 2, - "Glioma": 1, - "Head and Neck Cancer": 3, - "Hepatobiliary Cancer": 2, - "Non-Small Cell Lung Cancer": 14, - "Ovarian Epithelial Tumor": 1 + "Colorectal Cancer": 2 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "F11", - "transcriptId": "ENST00000403665", - "genomicLocationDescription": "Alterations in Exon Splice Enhancement Sites (ESE) affecting multiple exons", - "defaultEffect": "missense", - "comment": "Alters number of ESEs affecting transcription and causing aberrant splicing", - "context": "Largely found in cancer-related thrombosis", - "revisedProteinEffects": [ + }, { - "variant": "4:g.187208954G>A", - "genomicLocation": "4,187208954,187208954,G,A", - "transcriptId": "ENST00000403665", - "vepPredictedProteinEffect": "p.E565K", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.D526_G572del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266046_41266665del", + "genomicLocation": "3,41266046,41266665,GAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCCT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X16_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.M14_P154del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000403665.2:c.1693G>A", + "hgvsc": "ENST00000349496.5:c.47_466del", "confirmed": false, "references": [ { - "pubmedId": "21718436", - "referenceText": "Zucker et al., 2011" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 2 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -7349,10 +6824,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -7367,10 +6844,12 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 2 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -7378,29 +6857,31 @@ "therapeuticLevel": null }, { - "variant": "4:g.187201659G>A", - "genomicLocation": "4,187201659,187201659,G,A", - "transcriptId": "ENST00000403665", - "vepPredictedProteinEffect": "p.G350R", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.K343_E379del", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000403665.2:c.1060G>A", + "variant": "3:g.41266047_41266630del", + "genomicLocation": "3,41266047,41266630,AACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X16_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.E15_Q143del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.46_429del", "confirmed": false, "references": [ { - "pubmedId": "21718436", - "referenceText": "Zucker et al., 2011" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -7415,62 +6896,64 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Endometrial Cancer": 1 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, - "unknownVariantsCount": 1, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Endometrial Cancer": 1 + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null }, { - "variant": "4:g.187197405C>T", - "genomicLocation": "4,187197405,187197405,C,T", - "transcriptId": "ENST00000403665", - "vepPredictedProteinEffect": "p.P206S", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.A199_R252del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266049_41266557del", + "genomicLocation": "3,41266049,41266557,CCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X16_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.E15_H118del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000403665.2:c.616C>T", + "hgvsc": "ENST00000349496.5:c.48_356del", "confirmed": false, "references": [ { - "pubmedId": "21718436", - "referenceText": "Zucker et al., 2011" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -7485,10 +6968,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -7503,50 +6988,44 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "MSH2", - "transcriptId": "ENST00000233146", - "genomicLocationDescription": "Alterations on the ESE motifs cause skipping of exons", - "defaultEffect": "missense", - "comment": "Alters number of ESEs affecting transcription", - "context": "Affects splicing across multiple cancer types", - "revisedProteinEffects": [ + }, { - "variant": "2:g.47641421C>T", - "genomicLocation": "2,47641421,47641421,C,T", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.S269L", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.V265_Q314del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266050_41266639del", + "genomicLocation": "3,41266050,41266639,CAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X17_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.P16_A146del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000233146.2:c.806C>T", + "hgvsc": "ENST00000349496.5:c.51_440del", "confirmed": false, "references": [ { - "pubmedId": "16995940", - "referenceText": "Lastella et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 4, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 4 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -7561,11 +7040,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 3, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Mesothelioma": 1 + "Colorectal Cancer": 3 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -7581,11 +7060,11 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 4, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Mesothelioma": 1 + "Colorectal Cancer": 4 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -7594,38 +7073,32 @@ "therapeuticLevel": null }, { - "variant": "2:g.47641430C>T", - "genomicLocation": "2,47641430,47641430,C,T", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.A272V", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.V265_Q314del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266051_41266631del", + "genomicLocation": "3,41266051,41266631,AGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X17_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.P16_Q143del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000233146.2:c.815C>T", + "hgvsc": "ENST00000349496.5:c.51_431del", "confirmed": false, "references": [ { - "pubmedId": "16995940", - "referenceText": "Lastella et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 5, - "unknownVariantsCount": 1, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Cancer of Unknown Primary": 1, - "Endometrial Cancer": 1, - "Skin Cancer, Non-Melanoma": 1, - "Small Bowel Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Soft Tissue Sarcoma": 1 + "Colorectal Cancer": 2 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { @@ -7639,19 +7112,13 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 5, - "unknownVariantsCount": 1, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Endometrial Cancer": 1, - "Ovarian Cancer": 1, - "Renal Cell Carcinoma": 1, - "Small Bowel Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Soft Tissue Sarcoma": 1 + "Colorectal Cancer": 2 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, "tcga": { @@ -7665,51 +7132,43 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 7, - "unknownVariantsCount": 1, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Breast Cancer": 1, - "Cancer of Unknown Primary": 1, - "Endometrial Cancer": 1, - "Ovarian Cancer": 1, - "Renal Cell Carcinoma": 1, - "Skin Cancer, Non-Melanoma": 1, - "Small Bowel Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Soft Tissue Sarcoma": 1 + "Colorectal Cancer": 2 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null }, { - "variant": "2:g.47693802G>T", - "genomicLocation": "2,47693802,47693802,G,T", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.D506Y", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.G504Afs*3", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000233146.2:c.1516G>T", + "variant": "3:g.41266053_41266624del", + "genomicLocation": "3,41266053,41266624,ACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTA,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X18_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.D17_N141del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.52_423del", "confirmed": false, "references": [ { - "pubmedId": "16995940", - "referenceText": "Lastella et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 2 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -7729,7 +7188,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 1 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -7745,11 +7204,11 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 2, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Non-Small Cell Lung Cancer": 2 + "Colorectal Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -7758,31 +7217,30 @@ "therapeuticLevel": null }, { - "variant": "2:g.47693886C>T", - "genomicLocation": "2,47693886,47693886,C,T", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.R534C", - "vepPredictedVariantClassification": "Missense_Mutation", - "revisedProteinEffect": "p.G504Afs*3", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000233146.2:c.1600C>T", + "variant": "3:g.41266054_41266649del", + "genomicLocation": "3,41266054,41266649,CAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X18_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.D17_A149del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.53_448del", "confirmed": false, "references": [ { - "pubmedId": "16995940", - "referenceText": "Lastella et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 4, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Endometrial Cancer": 1, - "Melanoma": 3 + "Small Bowel Cancer": 2 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -7798,17 +7256,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 17, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 1, - "Cervical Cancer": 1, - "Colorectal Cancer": 1, - "Endometrial Cancer": 3, - "Melanoma": 7, - "Non-Small Cell Lung Cancer": 3, - "Soft Tissue Sarcoma": 1 + "Small Bowel Cancer": 2 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -7824,17 +7276,11 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 17, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Cancer of Unknown Primary": 1, - "Cervical Cancer": 1, - "Colorectal Cancer": 1, - "Endometrial Cancer": 3, - "Melanoma": 7, - "Non-Small Cell Lung Cancer": 3, - "Soft Tissue Sarcoma": 1 + "Small Bowel Cancer": 2 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -7843,79 +7289,50 @@ "therapeuticLevel": null }, { - "variant": "2:g.47641560A>T", - "genomicLocation": "2,47641560,47641560,A,T", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.X314_splice", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.V265_Q314del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "variant": "3:g.41266059_41266307del", + "genomicLocation": "3,41266059,41266307,AAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X19_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.K19_D81del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000233146.2:c.942+3A>T", + "hgvsc": "ENST00000349496.5:c.56_241+63del", "confirmed": false, "references": [ { - "pubmedId": "33259954", - "referenceText": "Oldfield et al., 2021" - }, - { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { - "germlineVariantsCount": 21, - "somaticVariantsCount": 3, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Bladder Cancer": 2, - "Bone Cancer": 1, - "Colorectal Cancer": 7, - "Endometrial Cancer": 4, - "Miscellaneous Neuroepithelial Tumor": 1, - "Pancreatic Cancer": 1, - "Prostate Cancer": 1, - "Small Bowel Cancer": 1, - "Soft Tissue Sarcoma": 2, - "Tubular Adenoma of the Colon": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 1, - "Esophagogastric Cancer": 1, - "Thyroid Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 7, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Colorectal Cancer": 2, - "Endometrial Cancer": 1, - "Esophagogastric Cancer": 1, - "Glioma": 1, - "Ovarian Cancer": 1, - "Thyroid Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -7930,29 +7347,12 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 20, - "somaticVariantsCount": 9, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Bladder Cancer": 2, - "Colorectal Cancer": 7, - "Endometrial Cancer": 4, - "Miscellaneous Neuroepithelial Tumor": 1, - "Pancreatic Cancer": 1, - "Prostate Cancer": 1, - "Small Bowel Cancer": 1, - "Soft Tissue Sarcoma": 2, - "Tubular Adenoma of the Colon": 1 - }, + "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Bone Cancer": 1, - "Colorectal Cancer": 2, - "Endometrial Cancer": 1, - "Esophagogastric Cancer": 1, - "Glioma": 1, - "Melanoma": 1, - "Ovarian Cancer": 1, - "Thyroid Cancer": 1 + "Hepatobiliary Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 @@ -7961,38 +7361,31 @@ "therapeuticLevel": null }, { - "variant": "2:g.47693952G>C", - "genomicLocation": "2,47693952,47693952,G,C", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.*554*", - "vepPredictedVariantClassification": "Splice_Region", - "revisedProteinEffect": "p.G504Afs*3", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000233146.2:c.1661+5G>C", + "variant": "3:g.41266057_41266652del", + "genomicLocation": "3,41266057,41266652,AAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCAC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X19_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.R18_T150del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.55_450del", "confirmed": false, "references": [ { - "pubmedId": "33259954", - "referenceText": "Oldfield et al., 2021" - }, - { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -8007,10 +7400,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -8025,10 +7420,12 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -8036,34 +7433,31 @@ "therapeuticLevel": null }, { - "variant": "2:g.47637512G>T", - "genomicLocation": "2,47637512,47637512,G,T", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.X215_splice", + "variant": "3:g.41266061_41266656del", + "genomicLocation": "3,41266061,41266656,GCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X20_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.A123_Q215del", - "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedProteinEffect": "p.K19_R151del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", "revisedStandardVariantClassification": "In_Frame_Del", - "hgvsc": "ENST00000233146.2:c.645+1G>T", + "hgvsc": "ENST00000349496.5:c.60_455del", "confirmed": false, "references": [ { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -8078,10 +7472,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -8096,10 +7492,12 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -8107,34 +7505,31 @@ "therapeuticLevel": null }, { - "variant": "2:g.47703711G>C", - "genomicLocation": "2,47703711,47703711,G,C", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.X737_splice", + "variant": "3:g.41266064_41266656del", + "genomicLocation": "3,41266064,41266656,GCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X21_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.G669Gfs*7", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000233146.2:c.2210+1G>C", + "revisedProteinEffect": "p.A20_R151del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.63_455del", "confirmed": false, "references": [ { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 2 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -8149,10 +7544,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 2 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -8167,10 +7564,12 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 2, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 2 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -8178,34 +7577,31 @@ "therapeuticLevel": null }, { - "variant": "2:g.47708011G>A", - "genomicLocation": "2,47708011,47708011,G,A", - "transcriptId": "ENST00000233146", - "vepPredictedProteinEffect": "p.X878_splice", + "variant": "3:g.41266065_41266501del", + "genomicLocation": "3,41266065,41266501,CTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X22_splice", "vepPredictedVariantClassification": "Splice_Site", - "revisedProteinEffect": "p.G820Afs*2", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000233146.2:c.2634+1G>A", + "revisedProteinEffect": "p.A21_P100del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.65_301del", "confirmed": false, "references": [ { - "pubmedId": "12362047", - "referenceText": "Kurzawski et al., 2002" - }, - { - "pubmedId": "16451135", - "referenceText": "Kurzawski et al., 2006" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -8224,7 +7620,7 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Endometrial Cancer": 1 + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -8244,51 +7640,40 @@ "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Endometrial Cancer": 1 + "Small Bowel Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "RB1", - "transcriptId": "ENST00000267163", - "genomicLocationDescription": "c.1206C>T mutation on exon 12", - "defaultEffect": "synonymous", - "comment": "Disrupting the splicing enhancer element and caused skipping of exon 12", - "context": "Reported in an individual with unilateral retinoblastoma", - "revisedProteinEffects": [ + }, { - "variant": "13:g.48947619C>T", - "genomicLocation": "13,48947619,48947619,C,T", - "transcriptId": "ENST00000267163", - "vepPredictedProteinEffect": "p.S402=", - "vepPredictedVariantClassification": "Silent", - "revisedProteinEffect": "p.R376Rfs*4", - "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", - "revisedStandardVariantClassification": "Frame_Shift_Del", - "hgvsc": "ENST00000267163.4:c.1206C>T", + "variant": "3:g.41266063_41266577del", + "genomicLocation": "3,41266063,41266577,GGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X22_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A20_L125del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.65_379del", "confirmed": false, "references": [ { - "pubmedId": "21763628", - "referenceText": "Ahani et al., 2011" + "pubmedId": "0", + "referenceText": "Pending" } ], - "variantNote": "This heterozygous RB1 c.1206C>T variant is a synonymous variant that does not alter the amino acid at this position (p.Ser402=). This variant has been identified in 3/30442 South Asian chromosomes by the Genome Aggregation Database (gnomAD: http://gnomad.broadinstitute.org). It has been reported in an individual with unilateral retinoblastoma and was demonstrated to cause abnormal splicing based on patient RNA studies (PMID 21763628). In our patient (DMG19-4863) with unilateral retinoblastoma, tumor analysis identified somatic biallelic mutations (two somatic hits) in RB1 (DMG internal data). In summary, based on the currently available data, the clinical significance of the RB1 c.1206C>T (p.Ser402=) variant is uncertain.", "counts": { "mskimpact": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Retinoblastoma": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -8303,10 +7688,12 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -8320,260 +7707,66 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 0, + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": { - "Retinoblastoma": 1 + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, - "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - } - ] - }, - { - "hugoGeneSymbol": "TERT", - "transcriptId": "ENST00000310581", - "genomicLocationDescription": "−124 bp from the ATG start site in the TERT promoter", - "defaultEffect": "non-coding", - "comment": "Creates new Ets/TCF binding site, increases TERT expression", - "context": "Found in many cancer types, such as glioma, bladder, thyroid, liver, melanoma", - "revisedProteinEffects": [ + }, { - "variant": "5:g.1295228G>A", - "genomicLocation": "5,1295228,1295228,G,A", - "transcriptId": "ENST00000310581", - "vepPredictedProteinEffect": null, - "vepPredictedVariantClassification": "5'Flank", - "revisedProteinEffect": null, - "revisedVariantClassification": null, - "revisedStandardVariantClassification": null, - "hgvsc": null, + "variant": "3:g.41266074_41266266del", + "genomicLocation": "3,41266074,41266266,ACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X24_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.H24_D81del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.71_241+22del", "confirmed": false, "references": [ { - "pubmedId": "24657534", - "referenceText": "Heidenreich et al., 2013" + "pubmedId": "0", + "referenceText": "Pending" } ], - "mutationOrigin": "somatic", - "variantNote": "−124C > T (this mutation) and −146C > T are the most common mutations. In melanoma −146C > T mutation is more frequent than the −124C > T; in cancers, especially in gliomas, thyroid cancers and bladder cancers the latter is the most common mutation.", "counts": { "mskimpact": { - "germlineVariantsCount": 6, - "somaticVariantsCount": 5585, - "unknownVariantsCount": 49, - "germlineVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Bone Cancer": 1, - "Glioma": 2, - "Melanoma": 2 - }, - "somaticVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 4, - "Ampullary Cancer": 6, - "Anal Cancer": 5, - "Bladder Cancer": 1641, - "Bone Cancer": 29, - "Breast Cancer": 33, - "Breast Sarcoma": 16, - "CNS Cancer": 7, - "Cancer of Unknown Primary": 160, - "Cervical Cancer": 28, - "Choroid Plexus Tumor": 2, - "Colorectal Cancer": 45, - "Embryonal Tumor": 16, - "Endometrial Cancer": 35, - "Esophagogastric Cancer": 8, - "Gastrointestinal Neuroendocrine Tumor": 2, - "Gastrointestinal Stromal Tumor": 3, - "Germ Cell Tumor": 1, - "Glioma": 1257, - "Head and Neck Cancer": 152, - "Hepatobiliary Cancer": 270, - "Medulloblastoma": 1, - "Melanoma": 553, - "Mesothelioma": 26, - "Miscellaneous Brain Tumor": 4, - "Miscellaneous Neuroepithelial Tumor": 4, - "Neoplastic Vs Reactive": 7, - "Nerve Sheath Tumor": 2, - "Non-Small Cell Lung Cancer": 178, - "Ovarian Cancer": 56, - "Pancreatic Cancer": 10, - "Penile Cancer": 8, - "Peripheral Nervous System": 8, - "Peritoneal Cancer, NOS": 2, - "Pheochromocytoma": 1, - "Prostate Cancer": 5, - "Renal Cell Carcinoma": 130, - "Salivary Gland Cancer": 29, - "Sellar Tumor": 1, - "Sex Cord Stromal Tumor": 39, - "Skin Cancer, Non-Melanoma": 52, - "Small Bowel Cancer": 9, - "Small Cell Lung Cancer": 5, - "Soft Tissue Sarcoma": 187, - "Thyroid Cancer": 508, - "Tubular Adenoma of the Colon": 1, - "Uterine Sarcoma": 10, - "Vaginal Cancer": 21, - "Wilms Tumor": 5 - }, - "unknownVariantsCountByCancerType": { - "Bladder Cancer": 10, - "Breast Sarcoma": 1, - "CNS Cancer": 1, - "Choroid Plexus Tumor": 1, - "Glioma": 6, - "Head and Neck Cancer": 1, - "Hepatobiliary Cancer": 2, - "Mature B-Cell Neoplasms": 3, - "Melanoma": 7, - "Non-Small Cell Lung Cancer": 3, - "Soft Tissue Sarcoma": 9, - "Thyroid Cancer": 5 + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 1112, - "unknownVariantsCount": 11, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 2, - "Ampullary Cancer": 2, - "Anal Cancer": 1, - "Bladder Cancer": 208, - "Bone Cancer": 6, - "Breast Cancer": 8, - "Breast Sarcoma": 6, - "CNS Cancer": 1, - "Cancer of Unknown Primary": 30, - "Cervical Cancer": 8, - "Colorectal Cancer": 8, - "Embryonal Tumor": 3, - "Endometrial Cancer": 4, - "Gastrointestinal Stromal Tumor": 1, - "Germ Cell Tumor": 1, - "Glioma": 358, - "Head and Neck Cancer": 30, - "Hepatobiliary Cancer": 62, - "Melanoma": 97, - "Mesothelioma": 4, - "Miscellaneous Brain Tumor": 1, - "Non-Small Cell Lung Cancer": 29, - "Ovarian Cancer": 9, - "Pancreatic Cancer": 3, - "Penile Cancer": 1, - "Peripheral Nervous System": 1, - "Prostate Cancer": 2, - "Renal Cell Carcinoma": 26, - "Salivary Gland Cancer": 11, - "Sex Cord Stromal Tumor": 5, - "Skin Cancer, Non-Melanoma": 7, - "Small Bowel Cancer": 2, - "Small Cell Lung Cancer": 1, - "Soft Tissue Sarcoma": 36, - "Thyroid Cancer": 131, - "Uterine Sarcoma": 4, - "Vaginal Cancer": 2, - "Wilms Tumor": 1 - }, - "unknownVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Breast Sarcoma": 1, - "Choroid Plexus Tumor": 1, - "Hepatobiliary Cancer": 1, - "Mature B-Cell Neoplasms": 1, - "Non-Small Cell Lung Cancer": 1, - "Soft Tissue Sarcoma": 4, - "Thyroid Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 7917, - "unknownVariantsCount": 44, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 9, - "Ampullary Cancer": 6, - "Anal Cancer": 2, - "Appendiceal Cancer": 1, - "Bladder Cancer": 1580, - "Bone Cancer": 30, - "Breast Cancer": 45, - "Breast Sarcoma": 20, - "CNS Cancer": 22, - "Cancer of Unknown Primary": 274, - "Cervical Cancer": 26, - "Choroid Plexus Tumor": 6, - "Colorectal Cancer": 61, - "Desmoplastic/Nodular Medulloblastoma": 9, - "Embryonal Tumor": 50, - "Endometrial Cancer": 42, - "Esophagogastric Cancer": 8, - "Gastrointestinal Neuroendocrine Tumor": 2, - "Gastrointestinal Stromal Tumor": 3, - "Germ Cell Tumor": 2, - "Glioma": 2851, - "Head and Neck Cancer": 192, - "Hepatobiliary Cancer": 297, - "Leukemia": 2, - "Mature B-Cell Neoplasms": 22, - "Mature T and NK Neoplasms": 2, - "Medulloblastoma": 7, - "Melanocytoma": 1, - "Melanoma": 835, - "Mesothelioma": 29, - "Miscellaneous Brain Tumor": 11, - "Miscellaneous Neuroepithelial Tumor": 4, - "Myelodysplastic/Myeloproliferative Neoplasms": 1, - "Nerve Sheath Tumor": 4, - "Non-Small Cell Lung Cancer": 266, - "Other Cancer": 1, - "Ovarian Cancer": 62, - "Pancreatic Cancer": 13, - "Penile Cancer": 3, - "Peripheral Nervous System": 4, - "Peritoneal Cancer, NOS": 2, - "Pheochromocytoma": 1, - "Prostate Cancer": 4, - "Renal Cell Carcinoma": 122, - "Salivary Gland Cancer": 30, - "Sellar Tumor": 1, - "Sex Cord Stromal Tumor": 49, - "Skin Cancer, Non-Melanoma": 73, - "Small Bowel Cancer": 5, - "Small Cell Lung Cancer": 7, - "Soft Tissue Sarcoma": 175, - "Thyroid Cancer": 594, - "UNKNOWN": 7, - "Uterine Sarcoma": 10, - "Vaginal Cancer": 26, - "Wilms Tumor": 6 - }, - "unknownVariantsCountByCancerType": { - "Bladder Cancer": 7, - "Breast Sarcoma": 1, - "CNS Cancer": 1, - "Choroid Plexus Tumor": 1, - "Glioma": 4, - "Head and Neck Cancer": 1, - "Hepatobiliary Cancer": 2, - "Mature B-Cell Neoplasms": 3, - "Melanoma": 7, - "Non-Small Cell Lung Cancer": 3, - "Soft Tissue Sarcoma": 9, - "Thyroid Cancer": 5 + "Colorectal Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, "tcga": { @@ -8586,157 +7779,6020 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 1, - "somaticVariantsCount": 9981, - "unknownVariantsCount": 49, - "germlineVariantsCountByCancerType": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "3:g.41266072_41266664del", + "genomicLocation": "3,41266072,41266664,TCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCC,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X24_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.S23_P154del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.70_462del", + "confirmed": false, + "references": [ + { + "pubmedId": "0", + "referenceText": "Pending" + } + ], + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "3:g.41266079_41266629del", + "genomicLocation": "3,41266079,41266629,CAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTAT,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X26_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.W25_Y142del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.78_428del", + "confirmed": false, + "references": [ + { + "pubmedId": "0", + "referenceText": "Pending" + } + ], + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Esophagogastric Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Esophagogastric Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Esophagogastric Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "3:g.41266086_41266249del", + "genomicLocation": "3,41266086,41266249,AGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAG,-", + "transcriptId": "ENST00000349496", + "vepPredictedProteinEffect": "X29_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.Q28_D81del", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000349496.5:c.86_241+8del", + "confirmed": false, + "references": [ + { + "pubmedId": "0", + "referenceText": "Pending" + } + ], + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Endometrial Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + 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This variant has been identified in <0.01% of Non-Finnish European chromosomes in the genome Aggregation Database (http://gnomad.broadinstitute.org). It has been reported in combination with another pathogenic variant in individuals and families with Ataxia-telangiectasia (PMID: 9463314, 10980530, 9887333, 10330348, 19691550). It has also been reported in the heterozygous state in a BRCA1/2 negative individual undergoing multigene panel testing (PMID:26270727). An experimental study showed that this variant affects splicing and leads to exon skipping of exon 14 (PMID: 9887333). This variant is classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.). Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia.", + "counts": { + "mskimpact": { + "germlineVariantsCount": 8, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Cancer of Unknown Primary": 2, + "Colorectal Cancer": 1, + "Germ Cell Tumor": 1, + "Non-Small Cell Lung Cancer": 1, + "Pancreatic Cancer": 1, + "Prostate Cancer": 2 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1, + "Endometrial Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + 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"confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "11:g.108202764G>A", + "genomicLocation": "11,108202764,108202764,G,A", + "transcriptId": "ENST00000278616", + "vepPredictedProteinEffect": "p.X2596_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.L2544_E2596del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000278616.4:c.7788G>A", + "confirmed": true, + "references": [ + { + "pubmedId": "9792409", + "referenceText": "Broeks et al., 1998" + } + ], + "mutationOrigin": "germline", + "variantNote": "This heterozygous ATM c.7788G>A p.Glu2596Glu variant is a synonymous variant that occurs at the last nucleotide of exon 52 and does not alter the amino acid at this position. It has been identified in 0.002% of Non-Finnish European chromosomes by the Exome Aggregation Consortium (ExAC: http://exac.broadinstitute.org; dbSNP). This variant has been reported in two homozygous and one compound heterozygous individuals with ataxia-telangiectasia (PMID: 9792409 and 26693373). It has been demonstrated to cause altered splicing, leading to deletion of 53 amino acids in exon 52 (PMID: 9792409). This region includes part of the FAT domain, which has been suggested to be important for proper activity of the protein (PMID: 23532176, 25460276, 10782091, 27229179). In summary, based on the previous reports of this variant in individuals with ataxia-telangiectasia and its impact on the protein, this variant meets our criteria to be classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.) Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia.", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Small Bowel Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "11:g.108151895G>A", + "genomicLocation": "11,108151895,108151895,G,A", + "transcriptId": "ENST00000278616", + "vepPredictedProteinEffect": "p.X1192_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.S1135_K1192", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000278616.4:c.3576G>A", + "confirmed": true, + "references": [ + { + "pubmedId": "9887333", + "referenceText": "Sandoval et al., 1999" + }, + { + "pubmedId": "16941484", + "referenceText": "Cavalieri et al., 2006" + }, + { + "pubmedId": "21965147", + "referenceText": "Demuth et al., 2011" + } + ], + "mutationOrigin": "germline", + "variantNote": "This heterozygous ATM c.3576G>A variant is a synonymous alteration that does not change a Lysine to another amino acid at codon 1192 (p.Lys1192=). This variant occurs in the last nucleotide of an exon and leads to aberrant splicing leading to exon skipping according to in-vitro RNA studies (PMID: 9887333, 16941484, 21965147). This variant has been identified in 4/113572 of Non-Finnish European chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/;), and has been reported in multiple individuals with ataxia telangiectasia in heterozygous (in-trans with another pathogenic ATM variant) or homozygous states (PMID: 30819809, 8845835, 9443866, 9792409, 9887333, 10330348, 12552559, 16941484, 17124347). Furthermore, this variant has been detected in patients with breast, thyroid or ampullary cancers (PMID: 27599564, 30620386, 31300551). In summary, based on the previous reports of this variant in individuals with ATM associated disease and in-vitro functional studies, this variant is classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.) Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia.", + "counts": { + "mskimpact": { + "germlineVariantsCount": 3, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Colorectal Cancer": 1, + "Non-Small Cell Lung Cancer": 2 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Skin Cancer, Non-Melanoma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Non-Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 2, + "somaticVariantsCount": 3, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Non-Small Cell Lung Cancer": 2 + }, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1, + "Non-Small Cell Lung Cancer": 1, + "Skin Cancer, Non-Melanoma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + } + ] + }, + { + "hugoGeneSymbol": "BRCA1", + "transcriptId": "ENST00000357654", + "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", + "defaultEffect": "missense, splice, intron", + "comment": "Splice leads to frameshift", + "context": "", + "revisedProteinEffects": [ + { + "variant": "17:g.41197820C>T", + "genomicLocation": "17,41197820,41197820,C,T", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.X1823_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A1844Dfs*2", + "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000357654.3:c.5468-1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.41228505C>A", + "genomicLocation": "17,41228505,41228505,C,A", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.R1495M", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": "p.A1453Gfs*9", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000357654.3:c.4484G>T", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 4, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Breast Cancer": 1, + "Glioma": 1, + "Ovarian Cancer": 2 + }, + "somaticVariantsCountByCancerType": { + "Ovarian Cancer": 1, + "Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 7, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Non-Small Cell Lung Cancer": 3, + "Ovarian Cancer": 2, + "Pancreatic Cancer": 1, + "Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 4, + "somaticVariantsCount": 8, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Breast Cancer": 1, + "Glioma": 1, + "Ovarian Cancer": 2 + }, + "somaticVariantsCountByCancerType": { + "Non-Small Cell Lung Cancer": 3, + "Ovarian Cancer": 3, + "Pancreatic Cancer": 1, + "Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.41258474T>C", + "genomicLocation": "17,41258474,41258474,T,C", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.R71G", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": "p.C64*", + "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000357654:c.211A>G", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + }, + { + "pubmedId": "11385711", + "referenceText": "Vega et al., 2001" + } + ], + "variantNote": "The BRCA1 c.211A>G variant changes an arginine to glycine at codon 71 (p.R71G). This variant has been identified in 1/249744 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/), and has been reported as a founder mutation in the Spanish population shown to segregate with breast and ovarian cancer in multiple families (PMID: 11385711, 23683081, 27081505, 12014998, 20215541). According to RT-PCR analysis, this variants leads to an aberrantly spliced mRNA creating a premature stop codon (p.Cys64*) (PMID: 11385711, 19123044, 20215541, 21735045). Heterozygous truncating variants in BRCA1 are known to be pathogenic. Note: this variant is also known as 330A>G in the literature. The sequence analysis indicated that 22 base pairs of exon 4 were deleted, creating with the first bases of exon 5, a termination codon at position 64", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Ovarian Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Ovarian Cancer": 1, + "Pancreatic Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Ovarian Cancer": 1 + }, + "somaticVariantsCountByCancerType": { + "Ovarian Cancer": 1, + "Pancreatic Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.41258472C>T", + "genomicLocation": "17,41258472,41258472,C,T", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.X71_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.C64*", + "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000357654:c.212+1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "Deletion of 22 bp at the end of exon 4", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Cancer of Unknown Primary": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Cancer of Unknown Primary": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.41256985T>C", + "genomicLocation": "17,41256985,41256985,T,C", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.*71*", + "vepPredictedVariantClassification": "Intron", + "revisedProteinEffect": "p.R71Sfs*20", + "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Ins", + "hgvsc": "ENST00000357654:c.213-12A>G", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "Insertion of 11 bp of intro 4 at the beginning of exon 5", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Breast Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Breast Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "17:g.41234420C>A", + "genomicLocation": "7,116412044,116412044,G,A", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.X1453_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.R1397Yfs*2", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000357654:c.4357+1G>T", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "Skipping of exon 12", + "otherVariation": "Deletion of the first three bases of exon 14 (r.4358_4360del), leading to an in-frame deletion of the amino acid alanine at codon 1,453 (p.Ala1453del)", + "counts": {}, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.41234420del", + "genomicLocation": "17,41234420,41234420,C,-", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.X1453_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A1453Qfs*3", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000357654:c.4357+1delG", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "Deletion of a guanine at the last base of exon 12 (r.4357del) because of the use of a cryptic donor splice site created by the DNA mutation", + "otherVariation": "Can also be a a skipping of exon 13, although in the case of c.4357+1delG this aberrant band is observed in a lower proportion; this frameshift deletion is predicted to generate a premature stop codon (p.Arg1397TyrfsX2)", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.41228504C>A", + "genomicLocation": "17,41228504,41228504,C,A", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.X1495_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A1453Gfs*10", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000357654:c.4484+1G>T", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "This mutation arises in the invariant guanine in the consensus sequence of the 5' donor splice site of exon 13. cDNA analysis showed that this mutation abolishes the natural 5_ splice site of exon 13, causing complete deletion of this exon (r.4358_4484del)", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.41219622T>C", + "genomicLocation": "17,41219622,41219622,T,C", + "transcriptId": "ENST00000357654", + "vepPredictedProteinEffect": "p.*1692*", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.D1692Gfs*15", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Ins", + "hgvsc": "ENST00000357654:c.5074+3A>G", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "The BRCA1 c.5074+3A>G variant was identified in a woman with bilateral breast cancer; her mother, who was diagnosed with breast cancer at age 53 and with colorectal cancer at age 68, carried the same variant. RNA analysis of this variant shows an insertion of the first 153 bp of intron 16 (r.5074_5075ins5074+1_5074+153). the pathogenicity of this mutation may derive from the splicing anomalies detected and is supported by the co-segregation with breast cancer observed in this family.", + "otherVariation": "Can also be a skipping of exon 17 (r.4987_5074del), which is predicted to lead to the truncated proteins p.Val1665SerfsX8", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + } + ] + }, + { + "hugoGeneSymbol": "BRCA2", + "transcriptId": "ENST00000380152", + "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", + "defaultEffect": "splice, intron", + "comment": "Splice leads to frameshift", + "context": "", + "revisedProteinEffects": [ + { + "variant": "13:g.32900634A>G", + "genomicLocation": "13,32900634,32900634,A,G", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.X173_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.G173Sfs*17", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000380152.3:c.517-2A>G", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Melanoma": 1, + "Non-Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Melanoma": 1, + "Non-Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "13:g.32931878G>A", + "genomicLocation": "13,32931878,32931878,G,A", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.X2540_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.L2540Qfs*10", + "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000380152.3:c.7618-1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 3, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 1, + "Ovarian Cancer": 1, + "Pancreatic Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 3, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 1, + "Ovarian Cancer": 1, + "Pancreatic Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "13:g.32954050G>A", + "genomicLocation": "13,32954050,32954050,G,A", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.X3039_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.V2985Gfs*3", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000380152.3:c.9117G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 2, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Prostate Cancer": 2 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Bladder Cancer": 1, + "Skin Cancer, Non-Melanoma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 4, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 2, + "Colorectal Cancer": 1, + "Ovarian Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 2, + "somaticVariantsCount": 6, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Prostate Cancer": 2 + }, + "somaticVariantsCountByCancerType": { + "Bladder Cancer": 1, + "Breast Cancer": 2, + "Colorectal Cancer": 1, + "Ovarian Cancer": 1, + "Skin Cancer, Non-Melanoma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "13:g.32919384T>G", + "genomicLocation": "13,32919384,32919384,T,G", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.*2313*", + "vepPredictedVariantClassification": "Intron", + "revisedProteinEffect": "p.G2313Gfs*9", + "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Ins", + "hgvsc": "ENST00000380152.3:c.6937+594T>G", + "confirmed": false, + "references": [ + { + "pubmedId": "22753590", + "referenceText": "Anczuków et al., 2012" + } + ], + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "13:g.32900635G>A", + "genomicLocation": "13,32900635,32900635,G,A", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.X173_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.G173Sfs*19", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000380152.3:c.517-1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "Leads to a skipping of exon 7 (r.517_631del)", + "otherVariation": "Activate a cryptic donor splice site that leads to the skipping of most of exon 6 and all of exon 7 (r.478_631del). This transcript is predicted to lead to a truncated protein (p.Val160SerfsX19) ", + "counts": { + "mskimpact": { + "germlineVariantsCount": 2, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Pancreatic Cancer": 1, + "Prostate Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 2, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Pancreatic Cancer": 1, + "Prostate Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "13:g.32907378A>G", + "genomicLocation": "13,32907378,32907378,A,G", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.N588S", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": "p.N588_G637delinsS", + "revisedVariantClassification": "Splice_Exon_Shortening_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000380152.3:c.1763A>G", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "Identified in a woman diagnosed with breast cancer at age 31. This variant creates a new cryptic donor site, which leads to an alternative transcript consisting of an in-frame deletion of 147 nucleotides (r.1763_1909del) that, in turn, produces an in-frame deletion of 49 amino acids with the insertion of a serine (p.Asn588_Gly637delinsSer)", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "13:g.32944538G>A", + "genomicLocation": "13,32944538,32944538,G,A", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.X2778_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.I2778Yfs*15", + "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000380152.3:c.8332-1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "This mutation arises in the invariant dinucleotide in the consensus sequence of the 3_ acceptor splice site of exon 19. cDNA analysis of the mutation showed that this mutation abolishes the natural 3_ splice site of exon 19 and leads to the activation of a cryptic splice site 14 bp downstream. Consequently, the mutated transcript shows a 14-bp deletion at the beginning of exon 19 (r.8332_8345del).", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Esophagogastric Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Esophagogastric Cancer": 1, + "Melanoma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Esophagogastric Cancer": 1, "Melanoma": 1 }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "13:g.32953872T>G", + "genomicLocation": "13,32953872,32953872,T,G", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.*2985*", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.V2985Afs*8", + "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Ins", + "hgvsc": "ENST00000380152.3:c.8954-15T>G", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "It creates a new cryptic donor site that leads to an alternative transcript with an insertion of the last 14 nucleotides of intron 22 (r.8953_8954ins8954-14_8954-1), generating a truncated protein (p.Val2985AlafsX8). Segregation analysis showed that the two sisters with breast cancer (diagnosed at 29 and 40 years old, respectively) are carriers of this variant, which was inherited from their unaffected father whose history is non-informative of HBOCS.", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "13:g.32953882A>G", + "genomicLocation": "13,32953882,32953882,A,G", + "transcriptId": "ENST00000380152", + "vepPredictedProteinEffect": "p.X2985_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.V2985Dfs*34", + "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Ins", + "hgvsc": "ENST00000380152.3:c.8954-5A>G", + "confirmed": false, + "references": [ + { + "pubmedId": "21735045", + "referenceText": "Menéndez et al., 2012" + } + ], + "variantNote": "It creates a novel cryptic donor site that leads to an alternative transcript with an insertion of the last four nucleotides of intron 22 (r.8953_8954ins8954-4_8954-1), generating a truncated protein (p.Val2985AspfsX34). The variant was observed in a young female patient with metachronic bilateral cancer diagnosed at 36 and 42 years who has no relative affected by tumors associated with HBOCS.", + "counts": { + "mskimpact": { + "germlineVariantsCount": 2, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Endometrial Cancer": 1, + "Prostate Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 2, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Endometrial Cancer": 1, + "Prostate Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + } + ] + }, + { + "hugoGeneSymbol": "BRIP1", + "transcriptId": "ENST00000259008", + "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", + "defaultEffect": "splice", + "comment": "Skip exon 5", + "context": "Reported in individuals with breast and ovarian cancers", + "revisedProteinEffects": [ + { + "variant": "17:g.59926490C>T", + "genomicLocation": "17,59926490,59926490,C,T", + "transcriptId": "ENST00000259008", + "vepPredictedProteinEffect": "p.X169_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.D127Dfs*1", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000259008.2:c.507G>A", + "confirmed": true, + "references": [ + { + "pubmedId": "29368626", + "referenceText": "Weber-Lassalle et al., 2018" + } + ], + "mutationOrigin": "germline", + "variantNote": "This silent sequence change affects codon 169 of the BRIP1 mRNA and does not change the encoded amino acid sequence (p.Gln169=). This variant falls at the last nucleotide of BRIP1 exon 5. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD), and has been reported in the literature in individuals with breast and ovarian cancers (PMID: 29368626). An experimental study using patient RNA showed that this variant led to skipping of exon 5 and a prematurely truncated protein product (PMID: 29368626). In summary, although additional studies are required to fully establish its clinical significance, this BRIp1 c.507G>A p.Gln169= variant is classified as likely pathogenic. Heterozygous pathogenic variants in BRIP1 have been associated with an increased risk of ovarian cancer (PMID: 26315354, 2196457) and may increase the risk of breast cancer (PMID: 17033622). Biallelic mutations in BRIP1 have been associated with Fanconi Anemia, an autosomal recessive condition characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. If a BRIP1 mutation carrier's partner is heterozygous for a pathogenic BRIP1 mutation, there is a 25% risk that each child would be affected by Fanconi Anemia.", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Endometrial Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Non-Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Endometrial Cancer": 1 + }, + "somaticVariantsCountByCancerType": { + "Non-Small Cell Lung Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "17:g.59938807C>T", + "genomicLocation": "17,59938807,59938807,C,T", + "transcriptId": "ENST00000259008", + "vepPredictedProteinEffect": "p.X31_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.M1_S31del", + "revisedVariantClassification": "Splice_Exon_Skip_Non_Start", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000259008.2:c.93+1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + } + ] + }, + { + "hugoGeneSymbol": "CDH1", + "transcriptId": "ENST00000261769", + "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", + "defaultEffect": "missense, splice", + "comment": "Splice leads to frameshift(exon 11) and nonsense(exon 10)", + "context": "", + "revisedProteinEffects": [ + { + "variant": "16:g.68849663G>A", + "genomicLocation": "16,68849663,68849663,G,A", + "transcriptId": "ENST00000261769", + "vepPredictedProteinEffect": "p.X522_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.T523*", + "revisedVariantClassification": "Splice_Exon_Extension_Nonsense", + "revisedStandardVariantClassification": "Nonsense_Mutation", + "hgvsc": "ENST00000261769.5:c.1565+1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 12, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 3, + "Cancer of Unknown Primary": 1, + "Colorectal Cancer": 4, + "Esophagogastric Cancer": 3, + "Glioma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 20, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 6, + "Cancer of Unknown Primary": 1, + "Colorectal Cancer": 5, + "Endometrial Cancer": 1, + "Esophagogastric Cancer": 6, + "Glioma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 2, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": { + "Breast Cancer": 2 + }, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 21, + "unknownVariantsCount": 2, + "germlineVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 6, + "Cancer of Unknown Primary": 1, + "Colorectal Cancer": 5, + "Endometrial Cancer": 1, + "Esophagogastric Cancer": 7, + "Glioma": 1 + }, + "unknownVariantsCountByCancerType": { + "Breast Cancer": 2 + }, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "16:g.68845762G>A", + "genomicLocation": "16,68845762,68845762,G,A", + "transcriptId": "ENST00000261769", + "vepPredictedProteinEffect": "p.X336_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.S337Vfs*14", + "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Ins", + "hgvsc": "ENST00000261769.5:c.1008G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "8127895", + "referenceText": "Oda et al., 1994" + }, + { + "pubmedId": "18427545", + "referenceText": "Karam et al., 2008" + } + ], + "variantNote": "The heterozygous germline variant, CDH1 c.1008G>A (p.Glu336=) is located at the last nucleotide of exon 7 of the CDH1 gene. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD) and has been reported in an individual affected with diffuse gastric cancer (PMID: 27730413). Experimental studies and analysis of RNA demonstrated that this variant leads to aberrant splicing (PMID: 8127895, 18427545). Additionally, a different variant at this position (c.1008G>T) has been reported in a family affected with hereditary diffuse gastric cancer (PMID: 9537325, 19725995). In summary, although additional studies are required to fully establish its clinical significance, this c.1008G>A variant is classified as likely pathogenic.", + "otherVariation": "Can also be 25, 42, 150 bp intron 7 insertion, and whole intron 7 insertions", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Esophagogastric Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 1, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": { + "Breast Cancer": 1 + }, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 1, + "unknownVariantsCount": 1, + "germlineVariantsCountByCancerType": { + "Esophagogastric Cancer": 1 + }, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": { + "Breast Cancer": 1 + }, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "16:g.68853328G>A", + "genomicLocation": "16,68853328,68853328,G,A", + "transcriptId": "ENST00000261769", + "vepPredictedProteinEffect": "p.G571S", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": "p.Y523Ffs*15", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000261769.5:c.1711G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "B-Lymphoblastic Leukemia/Lymphoma": 1, + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 2, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "B-Lymphoblastic Leukemia/Lymphoma": 1, + "Colorectal Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + } + ] + }, + { + "hugoGeneSymbol": "CHEK2", + "transcriptId": "ENST00000328354", + "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", + "defaultEffect": "splice", + "comment": "Splice leads to frameshift", + "context": "", + "revisedProteinEffects": [ + { + "variant": "22:g.29121230C>T", + "genomicLocation": "22,29121230,29121230,C,T", + "transcriptId": "ENST00000328354", + "vepPredictedProteinEffect": "p.X148_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.E149Ifs*5", + "revisedVariantClassification": "Splice_Exon_Extension_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Ins", + "hgvsc": "ENST00000328354.6:c.444+1G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 13, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Bladder Cancer": 1, + "Breast Cancer": 2, + "Colorectal Cancer": 2, + "Glioma": 1, + "Melanoma": 2, + "Non-Small Cell Lung Cancer": 1, + "Pancreatic Cancer": 1, + "Peripheral Nervous System": 1, + "Prostate Cancer": 2 + }, + "somaticVariantsCountByCancerType": { + "Mesothelioma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 4, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 1, + "Glioma": 2, + "Mesothelioma": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 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splice sites predicted to alter splicing", + "defaultEffect": "splice", + "comment": "Splice leads to exon 9 or exon 6 skipping", + "context": "", + "revisedProteinEffects": [ + { + "variant": "16:g.23634452C>G", + "genomicLocation": "16,23634452,23634452,C,G", + "transcriptId": "ENST00000261584", + "vepPredictedProteinEffect": "p.X945_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A946_G999del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000261584.4:c.2835-1G>C", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + 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"unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Pancreatic Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + } + ] + }, + { + "hugoGeneSymbol": "RAD51D", + "transcriptId": "ENST00000590016", + "genomicLocationDescription": "Mutations at canonical splice sites predicted to alter splicing", + "defaultEffect": "splice", + "comment": "Splice leads to frameshift exon truncation", + "context": "", + "revisedProteinEffects": [ + { + "variant": "17:g.33428057T>A", + "genomicLocation": "17,33428057,33428057,T,A", + "transcriptId": "ENST00000590016", + "vepPredictedProteinEffect": "p.X302_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.P322Vfs*5", + "revisedVariantClassification": "Splice_Exon_Shortening_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000590016.1:c.964-2A>T", + "confirmed": false, + "references": [ + { + "pubmedId": "31843900", + "referenceText": "Casadei et al., 2019" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Endometrial Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Endometrial Cancer": 1 + }, + "somaticVariantsCountByCancerType": { + "Breast Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + } + ] + }, + { + "hugoGeneSymbol": "MLH1", + "transcriptId": "ENST00000231790", + "genomicLocationDescription": "Last nucleotide of exon 15;Alterations on the ESE motifs cause deletion of exons", + "defaultEffect": "splice", + "comment": "Skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation; Alters number of ESEs affecting transcription", + "context": "In Lynch syndrome colorectal cancer and multiple cancer types", + "revisedProteinEffects": [ + { + "variant": "3:g.37083822G>A", + "genomicLocation": "3,37083822,37083822,G,A", + "transcriptId": "ENST00000231790", + "vepPredictedProteinEffect": "p.X577_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.S556Rfs*13", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000231790.2:c.1731G>A", + "confirmed": true, + "references": [ + { + "pubmedId": "16341550", + "referenceText": "Pagenstecher et al., 2006" + }, + { + "pubmedId": "18561205", + "referenceText": "Tournier et al., 2008" + }, + { + "pubmedId": "16451135", + "referenceText": "Kurzawski et al., 2006" + } + ], + "mutationOrigin": "germline", + "variantNote": "The heterozygous germline variant, MLH1 c.1731G>A (p.Ser577Ser), results in a silent mutation and occurs at the last nucleotide of exon 15. This variant is absent from the major population databases (1000G, ESP and gnomAD). It is a well known pathogenic variant that has been reported in several individuals and families with Lynch syndrome (PMID: 16341550, 15849733, 20223024, 26300997, 14635101, 16216036, 16395668, 19669161). Experimental studies using mRNA isolated from patients blood as well as a reporter minigene assay showed that this variant results in the skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation (PMID: 16341550, 18561205, 16451135). In summary, based on the previous reports of this variant in individuals with MLH1 associated cancers and its truncating effect on the protein, this variant meets our criteria to be classified as pathogenic. Lynch syndrome is an autosomal dominant condition that confers an increased risk for colorectal cancer and endometrial cancers as well as other cancers. There is a 50% chance that each child would inherit this variant from a carrier parent.", + "counts": { + "mskimpact": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Pancreatic Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 6, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 5, + "Endometrial Cancer": 1 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 71283 + }, + "genie": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 7, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 4, + "Endometrial Cancer": 1, + "Glioma": 2 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 172005 + }, + "tcga": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 10953 + }, + "total": { + "germlineVariantsCount": 1, + "somaticVariantsCount": 13, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": { + "Pancreatic Cancer": 1 + }, + "somaticVariantsCountByCancerType": { + "Colorectal Cancer": 9, + "Endometrial Cancer": 2, + "Glioma": 2 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "3:g.37059048C>T", + "genomicLocation": "3,37059048,37059048,C,T", + "transcriptId": "ENST00000231790", + "vepPredictedProteinEffect": "p.A281V", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": 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"3:g.37090087G>C", + "genomicLocation": "3,37090087,37090087,G,C", + "transcriptId": "ENST00000231790", + "vepPredictedProteinEffect": "p.R659P", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": "p.E633_E663del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000231790.2:c.1976G>C", + "confirmed": false, + "references": [ + { + "pubmedId": "16995940", + "referenceText": "Lastella et al., 2006" + } + ], + "variantNote": "Alterations on the ESE motifs cause deletion of exons, affects splicing across multiple cancer types", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + 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} + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "3:g.37050394C>T", + "genomicLocation": "3,37050394,37050394,C,T", + "transcriptId": "ENST00000231790", + "vepPredictedProteinEffect": "p.X181_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.G181Gfs*20", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000231790.2:c.543C>T", + "confirmed": false, + "references": [ + { + "pubmedId": "28334867", + "referenceText": "Yamaguchi et al., 2017" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 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+ "totalPatientCount": 193482 + } + }, + "therapeuticLevel": "LEVEL_1" + }, + { + "variant": "3:g.37053309A>G", + "genomicLocation": "3,37053309,37053309,A,G", + "transcriptId": "ENST00000231790", + "vepPredictedProteinEffect": "p.X182_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.R84Sfs*5", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000231790.2:c.546-2A>G", + "confirmed": false, + "references": [ + { + "pubmedId": "16451135", + "referenceText": "Kurzawski et al., 2006" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 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"germlineVariantsCountByCancerType": { + "Colorectal Cancer": 1 + }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "3:g.37059089A>C", + "genomicLocation": "3,37059089,37059089,A,C", + "transcriptId": "ENST00000231790", + "vepPredictedProteinEffect": "p.S295R", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": "p.H264Lfs*1", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000231790.2:c.883A>C", + "confirmed": false, + "references": [ + { + "pubmedId": "12362047", + "referenceText": "Kurzawski et al., 2002" + }, + { + "pubmedId": "16451135", + "referenceText": "Kurzawski et al., 2006" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + 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"total": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "3:g.37067499G>C", + "genomicLocation": "3,37067499,37067499,G,C", + "transcriptId": "ENST00000231790", + "vepPredictedProteinEffect": "p.X470_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.T347Kfs*7", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000231790.2:c.1409+1G>C", + "confirmed": false, + "references": [ + { + "pubmedId": "12362047", + "referenceText": "Kurzawski et al., 2002" + }, + { + "pubmedId": "16451135", + "referenceText": "Kurzawski et al., 2006" + } + ], + "mutationOrigin": "germline", + "counts": { + "mskimpact": { + 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"7,55248980,55248981,-,TCCAGGAAGCCT", + "transcriptId": "ENST00000275493", + "vepPredictedProteinEffect": "p.X762_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.A763_Y764insFQEA", + "revisedVariantClassification": "Splice_Exon_Extension_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Ins", + "hgvsc": "ENST00000275493.2:c.2284-5_2290dup", + "confirmed": true, + "references": [ + { + "pubmedId": "31715539", + "referenceText": "Sousa et al., 2020" + } + ], + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 9, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Non-Small Cell Lung Cancer": 9 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + 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"therapeuticLevel": "LEVEL_1" + } + ] + }, + { + "hugoGeneSymbol": "TP53", + "transcriptId": "ENST00000269305", + "genomicLocationDescription": "c.375+5G mutations flanking exon 4", + "defaultEffect": "splice", + "comment": "Splice leads to whole exon 4 skipping inframe deletion or partial exon 4 skipping frameshift", + "context": "Recurrent in many cancer types and results in P53 protein loss of function", + "revisedProteinEffects": [ + { + "variant": "17:g.7579307C>A", + "genomicLocation": "17,7579307,7579307,C,A", + "transcriptId": "ENST00000269305", + "vepPredictedProteinEffect": "p.X125_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.S33_T125del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000269305.4:c.375+5G>T", + "confirmed": true, + "references": [ + { + "pubmedId": "34505757", + "referenceText": "Chui et al., 2021" + } + ], + "otherVariation": "Partial exon 4 skip, p.G59Vfs*23, Splice_Exon_Shortening_Frame_Shift", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 49, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Anal Cancer": 1, + "Bladder Cancer": 2, + "Breast Cancer": 3, + "Cancer of Unknown Primary": 3, + "Colorectal Cancer": 6, + "Endometrial Cancer": 2, + "Esophagogastric Cancer": 1, + "Glioma": 3, + "Non-Small Cell Lung Cancer": 10, + "Ovarian Cancer": 6, + "Pancreatic Cancer": 6, + "Peritoneal Cancer, NOS": 1, + "Sellar Tumor": 1, + "Small Cell Lung Cancer": 2, + "Soft Tissue Sarcoma": 2 + }, + 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"unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Anal Cancer": 1, + "Bladder Cancer": 2, + "Breast Cancer": 6, + "Cancer of Unknown Primary": 6, + "Colorectal Cancer": 12, + "Endometrial Cancer": 2, + "Esophagogastric Cancer": 5, + "Glioma": 5, + "Head and Neck Cancer": 1, + "Non-Small Cell Lung Cancer": 15, + "Ovarian Cancer": 6, + "Pancreatic Cancer": 7, + "Peritoneal Cancer, NOS": 1, + "Prostate Cancer": 1, + "Sellar Tumor": 1, + "Skin Cancer, Non-Melanoma": 2, + "Small Cell Lung Cancer": 2, + "Soft Tissue Sarcoma": 3 + }, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 193482 + } + }, + "therapeuticLevel": null + }, + { + "variant": "17:g.7579312C>A", + "genomicLocation": "17,7579312,7579312,C,A", + "transcriptId": "ENST00000269305", + "vepPredictedProteinEffect": "p.X125_splice", + "vepPredictedVariantClassification": "Splice_Region", + "revisedProteinEffect": "p.S33_T125del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000269305.4:c.375G>T", + "confirmed": true, + "references": [ + { + "pubmedId": "11420676", + "referenceText": "Varley et al., 2001" + } + ], + "mutationOrigin": "germline", + "variantNote": "The heterozygous germline variant, TP53 c.375G>T (Thr125=), is located at the last nucleotide of exon 4 of the TP53 gene. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD). It has been reported in a family with Li Fraumeni syndrome (PMID: 11420676). In vitro studies and analysis of RNA from patient cells demonstrated that this variant leads to aberrant splicing (PMID: 11420676, 25730903). Two other variants at this position (c.375G>A and c.375G>C) have been reported in individuals and families with Li Fraumeni syndrome (PMID: 9242456, 10864200, 11420676, 24382691, 31105275). In summary, although additional studies are required to fully establish its clinical significance, based on its previous report in an individual with Li Fraumeni syndrome and its demonstrated impact on splicing, this c.375G>T (p.?) variant is classified as likely pathogenic. Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome associated with an increased risk of tumors including soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias (http://www.ncbi.nlm.nih.gov/books/NBK1311/).", + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, + "totalPatientCount": 70067 + }, + "mskimpact_nonsignedout": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 124, + "unknownVariantsCount": 1, + "germlineVariantsCountByCancerType": {}, + "somaticVariantsCountByCancerType": { + "Adrenocortical Carcinoma": 1, + "Bladder Cancer": 4, + "Bone Cancer": 1, + "Breast Cancer": 3, + "Cancer of Unknown Primary": 5, + "Colorectal Cancer": 6, + "Endometrial Cancer": 1, + "Esophagogastric 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Splice Enhancement Sites (ESE) affecting multiple exons", + "defaultEffect": "missense", + "comment": "Alters number of ESEs affecting transcription and causing aberrant splicing", + "context": "Largely found in cancer-related thrombosis", + "revisedProteinEffects": [ + { + "variant": "4:g.187208954G>A", + "genomicLocation": "4,187208954,187208954,G,A", + "transcriptId": "ENST00000403665", + "vepPredictedProteinEffect": "p.E565K", + "vepPredictedVariantClassification": "Missense_Mutation", + "revisedProteinEffect": "p.D526_G572del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000403665.2:c.1693G>A", + "confirmed": false, + "references": [ + { + "pubmedId": "21718436", + "referenceText": "Zucker et al., 2011" + } + ], + "counts": { + "mskimpact": { + "germlineVariantsCount": 0, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, + "germlineVariantsCountByCancerType": {}, + 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"somaticVariantsCount": 3166, - "unknownVariantsCount": 3, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Adrenocortical Carcinoma": 2, - "Ampullary Cancer": 1, - "Anal Cancer": 5, - "Bladder Cancer": 392, - "Bone Cancer": 6, - "Breast Cancer": 15, - "Breast Sarcoma": 1, - "CNS Cancer": 11, - "Cancer of Unknown Primary": 97, - "Cervical Cancer": 13, - "Colorectal Cancer": 23, - "Desmoplastic/Nodular Medulloblastoma": 1, - "Embryonal Tumor": 4, - "Endometrial Cancer": 14, - "Esophagogastric Cancer": 7, - "Gastrointestinal Neuroendocrine Tumor": 1, - "Glioma": 1018, - "Head and Neck Cancer": 94, - "Hepatobiliary Cancer": 22, - "Histiocytosis": 1, - "Leukemia": 1, - "Mature B-Cell Neoplasms": 2, - "Medulloblastoma": 1, - "Melanoma": 1057, - "Mesothelioma": 5, - "Miscellaneous Brain Tumor": 2, - "Neoplastic Vs Reactive": 1, - "Nerve Sheath Tumor": 1, - "Non-Small Cell Lung Cancer": 59, - "Ovarian Cancer": 16, - "Pancreatic Cancer": 4, - "Penile Cancer": 8, - "Prostate Cancer": 1, - "Renal Cell Carcinoma": 20, - "Salivary Gland Cancer": 17, - "Sex Cord Stromal Tumor": 8, - "Skin Cancer, Non-Melanoma": 87, - "Small Bowel Cancer": 4, - "Small Cell Lung Cancer": 4, - "Soft Tissue Sarcoma": 33, - "Thyroid Cancer": 92, - "UNKNOWN": 2, - "Vaginal Cancer": 13 - }, - "unknownVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Bone Cancer": 1, - "Glioma": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null }, { - "variant": "5:g.1295228_1295229delinsAA", - "genomicLocation": "5,1295228,1295229,GG,AA", - "transcriptId": "ENST00000310581", - "vepPredictedProteinEffect": null, - "vepPredictedVariantClassification": "5'Flank", - "revisedProteinEffect": null, - "revisedVariantClassification": null, - "revisedStandardVariantClassification": null, - "hgvsc": null, + "variant": "2:g.47637512G>T", + "genomicLocation": "2,47637512,47637512,G,T", + "transcriptId": "ENST00000233146", + "vepPredictedProteinEffect": "p.X215_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.A123_Q215del", + "revisedVariantClassification": "Splice_Exon_Skip_In_Frame", + "revisedStandardVariantClassification": "In_Frame_Del", + "hgvsc": "ENST00000233146.2:c.645+1G>T", "confirmed": false, "references": [ { - "pubmedId": "24657534", - "referenceText": "Heidenreich et al., 2013" + "pubmedId": "12362047", + "referenceText": "Kurzawski et al., 2002" + }, + { + "pubmedId": "16451135", + "referenceText": "Kurzawski et al., 2006" } ], - "mutationOrigin": "somatic", - "variantNote": "In melanoma two CC > TT tandem mutations affecting −124/−125 and −138/−139 residues were also detected with a combined frequency of 9%; this mutation augmented the evidence for the UV-origin of tumor specific nucleotide changes in melanoma", + "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 86, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Cancer of Unknown Primary": 3, - "Glioma": 1, - "Head and Neck Cancer": 2, - "Hepatobiliary Cancer": 1, - "Melanoma": 63, - "Non-Small Cell Lung Cancer": 1, - "Skin Cancer, Non-Melanoma": 12, - "Soft Tissue Sarcoma": 2 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, @@ -8922,20 +14086,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 100, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Cancer of Unknown Primary": 7, - "Head and Neck Cancer": 3, - "Hepatobiliary Cancer": 1, - "Melanoma": 70, - "Nerve Sheath Tumor": 1, - "Non-Small Cell Lung Cancer": 1, - "Skin Cancer, Non-Melanoma": 14, - "Soft Tissue Sarcoma": 2 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -8950,21 +14104,10 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 124, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Cancer of Unknown Primary": 8, - "Glioma": 1, - "Head and Neck Cancer": 3, - "Hepatobiliary Cancer": 1, - "Melanoma": 90, - "Nerve Sheath Tumor": 1, - "Non-Small Cell Lung Cancer": 1, - "Skin Cancer, Non-Melanoma": 15, - "Soft Tissue Sarcoma": 3 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } @@ -8972,44 +14115,35 @@ "therapeuticLevel": null }, { - "variant": "5:g.1295242_1295243delinsAA", - "genomicLocation": "5,1295242,1295243,GG,AA", - "transcriptId": "ENST00000310581", - "vepPredictedProteinEffect": null, - "vepPredictedVariantClassification": "5'Flank", - "revisedProteinEffect": null, - "revisedVariantClassification": null, - "revisedStandardVariantClassification": null, - "hgvsc": null, + "variant": "2:g.47703711G>C", + "genomicLocation": "2,47703711,47703711,G,C", + "transcriptId": "ENST00000233146", + "vepPredictedProteinEffect": "p.X737_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.G669Gfs*7", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000233146.2:c.2210+1G>C", "confirmed": false, "references": [ { - "pubmedId": "24657534", - "referenceText": "Heidenreich et al., 2013" + "pubmedId": "12362047", + "referenceText": "Kurzawski et al., 2002" + }, + { + "pubmedId": "16451135", + "referenceText": "Kurzawski et al., 2006" } ], - "mutationOrigin": "somatic", - "variantNote": "In melanoma two CC > TT tandem mutations affecting −124/−125 and −138/−139 residues were also detected with a combined frequency of 9%; this mutation augmented the evidence for the UV-origin of tumor specific nucleotide changes in melanoma", + "mutationOrigin": "germline", "counts": { "mskimpact": { "germlineVariantsCount": 0, - "somaticVariantsCount": 131, - "unknownVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 17, - "Breast Cancer": 1, - "Cancer of Unknown Primary": 6, - "Head and Neck Cancer": 1, - "Hepatobiliary Cancer": 1, - "Melanoma": 90, - "Skin Cancer, Non-Melanoma": 12, - "Soft Tissue Sarcoma": 1, - "Thyroid Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 }, "mskimpact_nonsignedout": { @@ -9023,24 +14157,11 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 160, - "unknownVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 12, - "Breast Cancer": 1, - "Cancer of Unknown Primary": 10, - "Head and Neck Cancer": 3, - "Hepatobiliary Cancer": 1, - "Melanoma": 116, - "Pancreatic Cancer": 1, - "Skin Cancer, Non-Melanoma": 13, - "Soft Tissue Sarcoma": 2, - "Thyroid Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, "tcga": { @@ -9054,49 +14175,38 @@ }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 206, - "unknownVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 22, - "Breast Cancer": 1, - "Cancer of Unknown Primary": 10, - "Head and Neck Cancer": 4, - "Hepatobiliary Cancer": 1, - "Melanoma": 146, - "Pancreatic Cancer": 1, - "Skin Cancer, Non-Melanoma": 17, - "Soft Tissue Sarcoma": 2, - "Thyroid Cancer": 1, - "UNKNOWN": 1 - }, - "unknownVariantsCountByCancerType": { - "Melanoma": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null }, { - "variant": "5:g.1295161T>G", - "genomicLocation": "5,1295161,1295161,T,G", - "transcriptId": "ENST00000310581", - "vepPredictedProteinEffect": null, - "vepPredictedVariantClassification": "5'Flank", - "revisedProteinEffect": null, - "revisedVariantClassification": null, - "revisedStandardVariantClassification": null, - "hgvsc": null, + "variant": "2:g.47708011G>A", + "genomicLocation": "2,47708011,47708011,G,A", + "transcriptId": "ENST00000233146", + "vepPredictedProteinEffect": "p.X878_splice", + "vepPredictedVariantClassification": "Splice_Site", + "revisedProteinEffect": "p.G820Afs*2", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000233146.2:c.2634+1G>A", "confirmed": false, "references": [ { - "pubmedId": "24657534", - "referenceText": "Heidenreich et al., 2013" + "pubmedId": "12362047", + "referenceText": "Kurzawski et al., 2002" + }, + { + "pubmedId": "16451135", + "referenceText": "Kurzawski et al., 2006" } ], "mutationOrigin": "germline", - "variantNote": "In a large melanoma pedigree where affected individuals presented a severe form of the disease with an early age of onset. The germline mutation was present in affected and absent in unaffected individuals in the family with the exception of one.", "counts": { "mskimpact": { "germlineVariantsCount": 0, @@ -9109,63 +14219,20 @@ }, "mskimpact_nonsignedout": { "germlineVariantsCount": 0, - "somaticVariantsCount": 169, - "unknownVariantsCount": 1, + "somaticVariantsCount": 0, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 45, - "Breast Cancer": 1, - "Breast Sarcoma": 1, - "Cancer of Unknown Primary": 3, - "Colorectal Cancer": 5, - "Endometrial Cancer": 2, - "Esophagogastric Cancer": 2, - "Glioma": 1, - "Head and Neck Cancer": 6, - "Hepatobiliary Cancer": 11, - "Melanoma": 28, - "Mesothelioma": 11, - "Non-Small Cell Lung Cancer": 8, - "Ovarian Cancer": 9, - "Pancreatic Cancer": 1, - "Prostate Cancer": 1, - "Renal Cell Carcinoma": 20, - "Salivary Gland Cancer": 2, - "Small Bowel Cancer": 2, - "Soft Tissue Sarcoma": 7, - "Tubular Adenoma of the Colon": 1, - "Uterine Sarcoma": 1, - "Vaginal Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Bladder Cancer": 1 - }, + "somaticVariantsCountByCancerType": {}, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 71283 }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 73, + "somaticVariantsCount": 1, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Bladder Cancer": 12, - "Breast Cancer": 2, - "Cancer of Unknown Primary": 4, - "Cervical Cancer": 1, - "Colorectal Cancer": 4, - "Endometrial Cancer": 2, - "Esophagogastric Cancer": 1, - "Glioma": 3, - "Head and Neck Cancer": 3, - "Hepatobiliary Cancer": 3, - "Melanoma": 18, - "Mesothelioma": 2, - "Myelodysplastic Syndromes": 1, - "Non-Small Cell Lung Cancer": 6, - "Ovarian Cancer": 1, - "Pancreatic Cancer": 2, - "Renal Cell Carcinoma": 7, - "Salivary Gland Cancer": 1 + "Endometrial Cancer": 1 }, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 @@ -9173,79 +14240,62 @@ "tcga": { "germlineVariantsCount": 0, "somaticVariantsCount": 0, - "unknownVariantsCount": 4, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": {}, - "unknownVariantsCountByCancerType": { - "Hepatobiliary Cancer": 4 - }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 10953 }, "total": { "germlineVariantsCount": 0, - "somaticVariantsCount": 242, - "unknownVariantsCount": 5, + "somaticVariantsCount": 1, + "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, "somaticVariantsCountByCancerType": { - "Bladder Cancer": 57, - "Breast Cancer": 3, - "Breast Sarcoma": 1, - "Cancer of Unknown Primary": 7, - "Cervical Cancer": 1, - "Colorectal Cancer": 9, - "Endometrial Cancer": 4, - "Esophagogastric Cancer": 3, - "Glioma": 4, - "Head and Neck Cancer": 9, - "Hepatobiliary Cancer": 14, - "Melanoma": 46, - "Mesothelioma": 13, - "Myelodysplastic Syndromes": 1, - "Non-Small Cell Lung Cancer": 14, - "Ovarian Cancer": 10, - "Pancreatic Cancer": 3, - "Prostate Cancer": 1, - "Renal Cell Carcinoma": 27, - "Salivary Gland Cancer": 3, - "Small Bowel Cancer": 2, - "Soft Tissue Sarcoma": 7, - "Tubular Adenoma of the Colon": 1, - "Uterine Sarcoma": 1, - "Vaginal Cancer": 1 - }, - "unknownVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Hepatobiliary Cancer": 4 + "Endometrial Cancer": 1 }, + "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 } }, "therapeuticLevel": null - }, + } + ] + }, + { + "hugoGeneSymbol": "RB1", + "transcriptId": "ENST00000267163", + "genomicLocationDescription": "c.1206C>T mutation on exon 12", + "defaultEffect": "synonymous", + "comment": "Disrupting the splicing enhancer element and caused skipping of exon 12", + "context": "Reported in an individual with unilateral retinoblastoma", + "revisedProteinEffects": [ { - "variant": "5:g.1295349A>G", - "genomicLocation": "5,1295349,1295349,A,G", - "transcriptId": "ENST00000310581", - "vepPredictedProteinEffect": null, - "vepPredictedVariantClassification": "5'Flank", - "revisedProteinEffect": null, - "revisedVariantClassification": null, - "revisedStandardVariantClassification": null, - "hgvsc": null, + "variant": "13:g.48947619C>T", + "genomicLocation": "13,48947619,48947619,C,T", + "transcriptId": "ENST00000267163", + "vepPredictedProteinEffect": "p.S402=", + "vepPredictedVariantClassification": "Silent", + "revisedProteinEffect": "p.R376Rfs*4", + "revisedVariantClassification": "Splice_Exon_Skip_Frame_Shift", + "revisedStandardVariantClassification": "Frame_Shift_Del", + "hgvsc": "ENST00000267163.4:c.1206C>T", "confirmed": false, "references": [ { - "pubmedId": "24657534", - "referenceText": "Heidenreich et al., 2013" + "pubmedId": "21763628", + "referenceText": "Ahani et al., 2011" } ], - "variantNote": "Bladder cancer patients with TERT promoter mutations in tumors showed almost two-fold decreased survival and increased disease recurrence in the absence but not in the presence of the variant allele for the rs2853669 polymorphism (PMID: 24101484)", + "variantNote": "This heterozygous RB1 c.1206C>T variant is a synonymous variant that does not alter the amino acid at this position (p.Ser402=). This variant has been identified in 3/30442 South Asian chromosomes by the Genome Aggregation Database (gnomAD: http://gnomad.broadinstitute.org). It has been reported in an individual with unilateral retinoblastoma and was demonstrated to cause abnormal splicing based on patient RNA studies (PMID 21763628). In our patient (DMG19-4863) with unilateral retinoblastoma, tumor analysis identified somatic biallelic mutations (two somatic hits) in RB1 (DMG internal data). In summary, based on the currently available data, the clinical significance of the RB1 c.1206C>T (p.Ser402=) variant is uncertain.", "counts": { "mskimpact": { - "germlineVariantsCount": 0, + "germlineVariantsCount": 1, "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": {}, + "germlineVariantsCountByCancerType": { + "Retinoblastoma": 1 + }, "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 70067 @@ -9261,14 +14311,10 @@ }, "genie": { "germlineVariantsCount": 0, - "somaticVariantsCount": 3, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Hepatobiliary Cancer": 1, - "Miscellaneous Brain Tumor": 1 - }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 172005 }, @@ -9282,15 +14328,13 @@ "totalPatientCount": 10953 }, "total": { - "germlineVariantsCount": 0, - "somaticVariantsCount": 3, + "germlineVariantsCount": 1, + "somaticVariantsCount": 0, "unknownVariantsCount": 0, - "germlineVariantsCountByCancerType": {}, - "somaticVariantsCountByCancerType": { - "Bladder Cancer": 1, - "Hepatobiliary Cancer": 1, - "Miscellaneous Brain Tumor": 1 + "germlineVariantsCountByCancerType": { + "Retinoblastoma": 1 }, + "somaticVariantsCountByCancerType": {}, "unknownVariantsCountByCancerType": {}, "totalPatientCount": 193482 }