Background
Methods
Study population
Targeted sequencing
Sequencing data analysis
Nomenclature and classification of genetic variants
In silico analyses of VUS
Cell-based minigene splicing assays
Results
Clinical characteristics and family history
Patient_ID | Gender | ICD9 diagnosis (age) | AMS criteria | Revised Bethesda | Tumor molecular characteristics |
---|---|---|---|---|---|
3222 | F | CC (54), Hyperplastic polyp (55/61/62/63/65), BC (70) | 0 | Y | MMR IHC proficient |
3308 | F | CC (43), BC (51/52) | 0 | Y | MMR IHC proficient |
3387 | F | BC (40), OC (70), CC (80) | 0 | Y | MMR IHC proficient |
3426 | M | MM (39) | I & II | Y | na |
4932 | F | CC (34), EC (40), Hyperplastic polyp (43), BT (46) | I & II | Y | na |
5324 | F | M (52), CC (59), SMC (na), BC (72) | 0 | Y | na |
6174 | F | Hyperplastic polyp (63/67), BC (65) | I & II | Y | MMR IHC proficient |
6977 | F | TC (66) | 0 | Y | MMR IHC proficient |
9876 | F | M (45), BC (54) | 0 | Y | na |
9998 | F | Hyperplastic polyp (45), CC (45) | II | Y | MMR IHC proficient |
10,675 | F | BC (51), Hyperplastic polyp (59), TC (60) | II | Y | na |
12,954 | F | Hyperplastic polyp (69), ML (70) | II | Y | na |
13,072 | M | Hyperplastic polyp (63/64/65), CC (65/67) | 0 | Y | na |
14,930 | F | Hyperplastic polyp (86), CC (86) | 0 | Y | MMR IHC proficient |
18,843 | F | BC (44), CC (49), SMC (na) | 0 | Y | na |
19,411 | M | PC (70) | 0 | Y | MSH6 IHC deficient |
19,673 | F | BC (40/42) | II | Y | na |
20,612 | F | Hyperplastic polyp (59/65), EC (70) | 0 | Y | na |
21,368 | F | OC (62) | 0 | Y | na |
22,295 | F | Hyperplastic polyp (53), M (58) | 0 | Y | na |
23,761 | F | Hyperplastic polyp (40/42/44), BC (50) | 0 | Y | na |
23,910 | F | M (43), Hyperplastic polyp (49), BC (63), BT (63) | 0 | Y | na |
24,140 | F | CC (45/67), BC (56) | 0 | Y | na |
24,447 | F | BC (57/66), CC (66) | 0 | Y | MLH1/PMS2 IHC deficient and MSI |
11,705 | F | THC (53), KC (53/63) | II | Y | MMR IHC proficient |
12,673 | F | OC (23), SMC (36), RC (62) | II | Y | na |
13,393 | M | RC (48), CST (58) | I & II | Y | MMR IHC proficient and MSS |
14,963 | F | Hyperplastic polyp (69), BC (62) | 0 | Y | na |
19609a | F | CC (42), M (44), BC (57) | 0 | Y | MMR IHC proficient |
22,953 | F | BC (53) | II | Y | na |
24,789 | F | CC (43), RC (65), BC (72) | I & II | Y | MMR IHC proficient and MSS |
25,167 | M | CC (55) | I & II | Y | MMR IHC proficient |
5597 | M | Hyperplastic polyp (53/54), SC (55), KC (62) | 0 | Y | MMR IHC proficient |
8913 | F | Hyperplastic polyp (59), BC (61), TC (69) | 0 | Y | na |
Germline findings
Patient_ID | VUS (Class 3) | Benign or Likely Benign variants (Class 1 or 2) | Polymorphisms | Total variants/patient |
---|---|---|---|---|
3222 | NOTCH3 NM_000435: c.5854G >A, p.V1952 M(rs115582213)b POLE NM_006231: c.3046G > A, p.V1016 M (rs147692158) | ATM NM_000051: c.5071A > C, p.S1691R (rs1800059) BRCA1 NM_007300: c.5019G > A, p.M1673I (rs1799967) PALB2 NM_024675: c.2993G > A, p.G998E (rs45551636) PALB2 NM_024675: c.2014G > C, p.E672Q (rs45532440) | rs459552, rs659243, rs2240308, rs1799966, rs16942, rs16941, rs169547, rs4986764, rs1805107, rs506504, rs832582, rs5868032, rs1042821, rs3219484, rs1044009, rs152451, rs2228006, rs1805321, rs4796033, rs1042522, rs861539, rs13125836 | 28 |
3308 | NBN NM_002485: c.1720 T > A, p.L574I (rs142334798)POLE NM_006231:c.4523G > A, p.R1508H (rs142508245) | BARD1N M_000465: c.1075_1095del, p.L359-P365delLPECSSP (rs28997575) | rs459552, rs659243, rs11528010, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs702689, rs832582, rs5868032, rs1799977, rs1042821, rs3219484, rs1805794, rs1044009, rs2228006, rs5744934, rs5744751, rs4796033, rs1042522 | 24 |
3387 | na | CDKN2AN M_000077: c.442G > A, p.A148T (rs3731249) | rs459552, rs659243, rs1801516, rs2240308 rs2070094, rs2229571, rs11528010, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs3219489, rs1044009, rs2228006, rs1805321, rs5744934, rs1042522 | 23 |
3426 | na | na | rs459552, rs659243, rs1801516, rs2240308, rs2070094, rs2229571, rs1048108, rs11528010, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs1805794, rs1044009, rs2228006, rs1805321, rs1042522, rs13125836 | 23 |
4932 | NOTCH3 NM_000435: c.5854G >A, p.V1952 M (rs115582213)a STK11NM_00045:c.841C > A, p.P281T (rs377208033) | na | rs459552, rs659243, rs1801516, rs2240308, rs2229571, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs1805107, rs506504, rs12642536, rs702689, rs832582, rs5868032, rs3219489, rs1805794, rs1044009, rs2228006, rs1805321, rs861539 | 26 |
5324 | na | na | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs832582, rs1799977, rs3219489, rs1044009, rs2228006, rs1805321, rs5744934 | 19 |
6174 | na | PMS2 NM_000535: c.1454C > A, p.T485 K (rs1805323) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1048108, rs1799966, rs16942, rs16941, rs799917, rs4986850, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs3219484, rs1805794, rs1044009, rs2228006, rs1805321, rs1042522, rs861539 | 29 |
6977 | na | BARD1 NM_000465: c.1075_1095del, p.L359-P365delLPECSSP (rs28997575) BARD1NM_000465: c.1972C > T, p.R658C (rs3738888) BRCA2 NM_000059: c.9976A > T, p.K3326X (rs11571833) | rs459552, rs659243, rs1801516, rs2240308, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs3219489, rs1044009, rs2228006, rs5744934, rs1042522, rs861539, rs28908468 | 27 |
9876 | PSMC3IP NM_016556: c.136G > A, p.V46 M (rs757057684) RAD51B NM_133509: c.1063G > A, p.A355T (rs61758785) | RAD51D NM_002878: c.698A > G, p.E233G (rs28363284) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs169547, rs4986764, rs1805107, rs506504, rs702689, rs832582, rs5868032, rs1799977, rs1042821, rs1805794, rs1044009, rs2228006, rs1726801 | 21 |
9998 | na | MSH6 NM_000179: c.2633 T > C, p.V878A (rs2020912) | rs459552, rs659243, rs1801516, rs2240308, rs2070094, rs2229571, rs1048108, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs1044009, rs2228006, rs1805321, rs5744751, rs1042522 | 24 |
10,675 | na | PMS2 NM_000535: c.1531A > G, p.T511A (rs2228007) | rs459552, rs659243, rs1801516, rs2070094, rs2229571, rs11528010, rs1799966, rs16942, rs16941rs799917, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs702689, rs832582,rs5868032, rs1799977, rs1805794, rs1044009, rs2228006, rs10254120, rs1042522 | 26 |
12,954 | MUTYH NM_012222: c.812G > A, p.R271Q (rs149866955) RAD51C NM_058216: c.790G > A, p.G264S (rs147241704) | PMS2 NM_000535: c.1789A > T, p.T597S (rs1805318) | rs459552, rs659243, rs2240308, rs2229571, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs12642536, rs702689, rs832582, rs5868032, rs1044009, rs2228006, rs1805321, rs1726801, rs4796033, rs1042522 | 22 |
13,072 | BRCA1 NM_007300: c.4315C > T, p.L1439F (rs781260818) | PMS2 NM_000535: c.1531A > G, p.T511A (rs2228007) | rs459552, rs659243, rs1801516, rs2240308, rs2070094, rs2229571, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs1805794, rs1044009, rs2228006, rs5744751, rs1042522 | 29 |
14,930 | na | PALB2 NM_024675: c.925A > G, p.I309V (rs3809683) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1048108, rs1799966, rs16942, rs16941, rs799917, rs4986850, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs3219489, rs1805794, rs1044009, rs152451, rs2228006, rs1805321, rs5744934, rs1042522 | 30 |
18,843 | MSH6 NM_000179.2: c.2195G > A, p.R732Q (rs749746725) | BRCA1 NM_007300: c.3119G > A, p.S1040 N (rs4986852) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs11528010, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs832582, rs5868032, rs1799977, rs3219489, rs1044009, rs2228006, rs1805321, rs5744934, rs5744751, rs1042522, rs861539 | 26 |
19,411 | na | BARD1 NM_000465: c.1972C > T, p.R658C (rs3738888) PALB2 NM_024675: c.1010 T > C, p.L337S (rs45494092) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1799966, rs16942, rs16941, rs799917, rs4986850, rs144848, rs169547, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1805794, 1,044,009, rs2228006, rs1805321, rs5744751, rs1042522, rs861539 | 28 |
19,673 | AXIN2 NM_004655: c.344A > G, p.N115S (rs370257532) | APC NM_001127510: c.7504G > A, p.G2502S (rs2229995) PMS2 NM_000535: c.1454C > A, p.T485 K (rs1805323) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs702689, rs832582, rs5868032, rs1042821, rs1805794, rs1044009, rs2228006, rs1805321, rs4796033, rs1042522, rs861539, rs3218536 | 29 |
20,612 | na | CDKN2A NM_000077: c.442G > A, p.A148T (rs3731249) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs169547, rs4986764, rs1805107, rs506504, rs12642536, rs702689, rs5868032, rs1799977, rs1805794, rs1044009, rs2228006, rs1805321, rs10254120, rs5744934, rs4796033, rs1042522, rs861539 | 28 |
21,368 | MAP3K1 NM_005921: c.764A > G, p.N255S (rs56069227) | ATM NM_000051: c.2572 T > C, p.F858 L (rs1800056) | rs459552, rs659243, rs2240308, rs2229571, rs11528010, rs1799950, rs169547, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs1799977, rs1044009, rs2228006, rs1805321, rs5744934, rs4796033, rs1042522 | 22 |
22,295 | na | BRCA1 NM_007300: c.5019G > A, p.M1673I (rs1799967) BRIP1 NM_032043: c.890A > G, p.K297R (rs28997570) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1048108, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs1805107, rs506504, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs1042821, rs3219489, rs1805794, rs1044009, rs2228006, rs1805321, rs5744934, rs1042522, rs861539 | 30 |
23,761 | na | na | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs1799950, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs1799977, rs1044009, rs2228006, rs1805321, rs1802683, rs1042522 | 26 |
23,910 | na | BRCA2 NM_000059: c.6100C > T, p.R2034C (rs1799954) MSH2 NM_000251: c.965G > A, p.G322D (rs4987188) MSH6 NM_000179: c.2633 T > C, p.V878A (rs2020912) PALB2 NM_024675: c.2794G > A, p.V932 M (rs45624036) PMS2 NM_000535: c.1454C > A, p.T485 K (rs1805323) BARD1 NM_000465: c.1670G > C, p.C557S (rs28997576) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs11528010, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs1799977, rs1042821, rs1805794, rs2228006, rs10254120, rs1042522, rs13125836, rs3218536 | 28 |
24,140 | na | BRCA1 NM_007300: c.5019G > A, p.M1673I (rs1799967) PMS2 NM_000535: c.1531A > G, p.T511A (rs2228007) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1048108, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs1799977, rs1042821, rs3219489, rs1805794, rs1044009, rs2228006, rs10254120, rs5744751, rs1042522 | 29 |
24,447 | CHEK2 NM_007194: c.74 T > C, p.V25A (rs587780188) | NOTCH3 NM_000435: c.3399C > A, p.H1133Q (rs112197217) | rs459552, rs659243, rs1801516, rs2240308, rs2070094, rs2229571, rs1799966, rs16942, rs16941, rs799917, rs169547, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs1805794, rs1044009, rs2228006, rs1805321, rs1042522 | 24 |
11,705 | ATM NM_000051: c.4375G > A, p.G1459R (rs145667735) MSH2 NM_000251: c.1284C > G, p.H428Q (rs776034412) | MSH2 NM_000251: c.965G > A, p.G322D (rs4987188) PMS2 NM_000535: c.1454C > A, p.T485 K (rs1805323) | rs459552, rs659243, rs1801516, rs2229571, rs11528010, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs702689, rs832582 rs5868032, rs1799977, rs3219489, rs1805794, rs1044009, rs2228006, rs1805321, rs5744751, rs1042522, rs861539, rs13125836 | 27 |
12,673 | na | ATM NM_000051: c.2572 T > C, p.F858 L (rs1800056) PMS2 NM_000535: c.1454C > A, p.T485 K (rs1805323) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1048108, rs1799950, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs1044009, rs2228006, rs1805321, rs1802683, rs4796033, rs1042522, rs861539 | 26 |
13,393 | NBN NM_002485.4: c.643C > T, p.R215W (rs34767364) | BARD1 NM_000465: c.1972C > T, p.R658C (rs3738888) BRIP1 NM_032043: c.577G > A, p.V193I (rs4988346) PMS2 NM_000535: c.1531A > G, p.T511A (rs2228007) ATM NM_000051: c.4258C > T, p.L1420F (rs1800058) NOTCH3 NM_000435.2: c.3058G > C, p.A1020P (rs35769976) NOTCH3 NM_000435: c.3547G > A, p.V1183 M (rs10408676) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1799966, rs16942, rs16941, rs799917, rs169547, rs4986764, rs1805107, rs506504, rs702689, rs832582, rs5868032, rs1805794, rs1044009, rs2228006, rs1805321, rs1042522 | 28 |
14,963 | PALB2 NM_024675: c.232G > A, p.V78I (rs515726085) | PALB2 NM_024675: c.2590C > T, p.P864S (rs45568339) STK11 NM_000455: c.1062C > G, p.F354 L (rs59912467) | rs659243, rs1801516, rs2240308, rs2070094, rs2229571, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs1799950, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs5868032, rs1799977, rs3219489, rs1805794, rs1044009, rs2228006, rs1805321, rs5744751, rs1042522, rs861539, rs3218536 | 33 |
19,609a | na | BRCA2 NM_000059: c.4258G > T, p.D1420Y (rs28897727) POLE NM_006231: c.2083 T > A, p.F695I (rs5744799) | rs459552, rs659243, rs2240308, rs2229571, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs702689, rs832582, rs5868032, rs1799977, rs3219484, rs1805794, rs1044009, rs2228006, rs1805321, rs5744934, rs1042522, rs13125836 | 28 |
22,953 | NOTCH3 NM_000435: c.5208G > C, p.E1736D (rs200331646) MSH2 NM_000251: c.128A > G, p.Y43C (rs17217723) RAD51B NM_133510: c.515 T > G, p.L172 W (rs34094401) | BRCA2 NM_000059: c.2971A > G, p.N991D (rs1799944) CDH1 NM_004360: c.1774G > A, p.A592T (rs35187787) | rs459552, rs659243, rs2240308, rs2229571, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs169547, rs4986764, rs1805107, rs506504, rs12642536, rs702689, rs832582, rs5868032, rs1042821, rs3219489, rs1805794, rs1044009, rs2228006, rs1805321, rs1726801 | 29 |
24,789 | APC NM_001127510: c.4334C > T, p.T1445I (rs760686348) PALB2 NM_024675: c.1250C > A, p.S417Y (rs45510998) | BARD1 NM_000465: c.1972C > T, p.R658C (rs3738888) PALB2 NM_024675: c.2993G > A, p.G998E (rs45551636) PALB2 NM_024675: c.2014G > C, p.E672Q (rs45532440) POLE NM_006231: c.776G > A, p.R259H (rs61732929) NOTCH3 NM_000435: c.3399C > A, p.H1133Q (rs112197217) | rs459552, rs659243, rs2240308, rs2229571, rs1799966, rs16942, rs16941, rs799917, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs3219489, rs1044009, rs152451, rs2228006, rs1042522 | 30 |
25,167 | NBN NM_002485.4: c.643C > T, p.R215W (rs34767364) | ATM NM_000051: c.2119 T > C, p.S707P (rs4986761) | rs459552, rs659243, rs2240308, rs2229571, rs11528010, rs169547, rs4986764, rs1805107, rs506504, rs12642536, rs702689, rs832582, rs5868032, rs1799977, rs1805794, rs2228006, rs1805321, rs1726801, rs4796033, rs1042522 | 22 |
5597 | MAP3K1 NM_005921: c.2816C > G, p.S939C (rs45556841) | ATM NM_000051: c.5071A >C, p.S1691R (rs1800059) | rs459552, rs659243, rs1801516, rs2070094, rs2229571, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs4986850, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs12642536, rs702689, rs832582, rs5868032, rs1042821, rs1805794, rs1044009, rs2228006, rs1805321, rs1042522 | 29 |
8913 | RAD51B NM_133509: c.1063G > A, p.A355T (rs61758785) EPCAM NM_002354: c.267G > C, p.Q89H (rs146480420) | PMS2 NM_000535: c.1454C > A, p.T485 K (rs1805323) | rs459552, rs659243, rs2240308, rs2070094, rs2229571, rs1048108, rs11528010, rs1799966, rs16942, rs16941, rs799917, rs144848, rs169547, rs4986764, rs1805107, rs506504, rs1126497, rs702689, rs832582, rs5868032, rs1805794, rs1044009, rs2228006, rs5744751, rs1042522, rs861539, rs13125836 | 30 |
Protein and splicing-dedicated in silico analyses
Selected variants (VAR) | Reference splice site-dedicated analyses | Cryptic splice site-dedicated analyses | ESR-dedicated analyses |
Protein-dedicated analyses
| ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient_ID | Genomic position (GRCh37) | Gene | Exon | Nucleotide change (cNomen) | Predicted protein change (pNomen) | Nearest reference | MES scores | SSFL scores | Potential local splice effect | Local MES scores | ∆tESRseq |
∆Hzei
|
ΔΨ
| |||||||||||
splice site | WT | Var | VAR vs WT | WT | Var | VAR vs WT | WT | Var | ||||||||||||||||
Distance | Type |
∆ (%)
| ||||||||||||||||||||||
(nt) | (3’ or 5’ss) |
Δ (%)
|
AGVGD
|
SIFT
|
MAPP
|
PolyPhen-2
|
MutationTaster
| |||||||||||||||||
3222 & 4932 | chr19:15273335 C>T |
NOTCH3
|
32
|
c.5854G>A
|
p.V1952M
| 39 | 3’ | 11.5 | 11.5 | 0 | 89.2 | 89.2 | 0 | - | - | - |
-1.78501
|
-11.15
|
-0.89
| C15 | Deleterious | bad | probably damaging | disease causing |
3222 |
POLE
| 25 | c.3046G>A | p.V1016M | -15 | 5’ | 9.1 | 9.1 | 0 | 82.5 | 82.5 | 0 | - | - | - | -0.74478 | 1 | -0.43 | C0 | Deleterious | bad | benign | disease causing | |
3308 | chr8:90965597 A>T |
NBN
| 11 | c.1720T>A | p.L574I | -126 | 5’ | 8.0 | 8.0 | 0 | 82.4 | 82.4 | 0 | - | - | - | 1.97427 | 33.38 | 0.18 | C0 | Tolerated | good | benign | polymorphism |
chr12:133219838 C>T |
POLE
| 35 | c.4523G>A | p.R1508H | -29 | 5’ | 7.9 | 7.9 | 0 | 73.8 | 73.8 | 0 | - | - | - | -0.600279 | -3.17 | -0.08 | C0 | Tolerated | good | benign | disease causing | |
4932 | chr19:1221318 C>A |
STK11
| 6 | c.841C>A | p.P281T | -22 | 5’ | 6.0 | 6.0 | 0 | 79.9 | 79.9 | 0 | - | - | - | -0.17437 | 7.7 | -0.72 | C0 | Tolerated | good | benign | disease causing |
5597 | chr5:56177843 C>G |
MAP3K1
| 14 | c.2816C>G | p.S939C | 447 | 3’ | 12.0 | 12.0 | 0 | 100.0 | 100.0 | 0 | - | - | - | -0.486881 | -16.1 | 0 | C0 | Deleterious | good | benign | polymorphism |
9876 | chr17: 40729320 C>T |
PSMC3IP
| 3 | c.136G>A | p.V46M | 1 | 3’ | 12.5 | 11.7 | -6 | 87.5 | 83.6 | -4 | - | - | - | 2.0413 | 74.24 | -0.3 | C0 | Deleterious | - | possibly damaging | disease causing |
9876 & 8913 | chr14:69061228 G>A |
RAD51B
| 11* | c.1063G>A | p.A355T | 27 | 3’ | 11.8 | 11.8 | 0 | 80.2 | 80.2 | 0 | - | - | - | -1.24035 | -50.64 | - | C0 | Deleterious | - | benign | polymorphism |
12954 | chr1: 45797950_C>T |
MUTYH
| 10 | c.812G>A | p.R271Q | 33 | 3’ | 9.5 | 9.5 | 0 | 86.8 | 86.8 | 0 | - | - | - | -2.31042 | 0.88 | 0.09 | C35 | Deleterious | bad | possibly damaging | disease causing |
chr17:56787304 G>A |
RAD51C
| 5 | c.790G>A | p.G264S | -48 | 5’ | 8.6 | 8.6 | 0 | 75.4 | 75.4 | 0 | New Acceptor Site? | 0 | 2.5 | -1.71397 | -59.31 | -0.21 | C0 | Tolerated | good | benign | disease causing | |
13072 | chr17:41234463 G>A |
BRCA1
| 12 | c.4315C>T | p.L1439F | -43 | 5’ | 6.6 | 6.6 | 0 | 85.2 | 85.2 | 0 | - | - | - | -0.261141 | 8.83 | -2.67 | C0 | Tolerated | good | benign | polymorphism |
18843 | chr2:48027317 G>A |
MSH6
| 4** | c.2195G>A | p.R732Q | -978 | 5’ | 8.9 | 8.9 | 0 | 81.6 | 81.6 | 0 | - | - | - | -0.805417 | -13.15 | 0 | C0 | Tolerated | good | benign | disease causing |
19673 | chr17:63554395 T>C |
AXIN2
| 2 | c.344A>G | p.N115S | 460 | 3’ | 11.1 | 11.1 | 0 | 93.3 | 93.3 | 0 | New Acceptor Site? | 11.1 | 7.2 | -0.162849 | -2.19 | -0.05 | C0 | Tolerated | good | benign | disease causing |
21368 | chr5:56155672 A>G |
MAP3K1
|
3
|
c.764A>G
|
p.N255S
| -71 | 5’ | 7.5 | 7.5 | 0 | 78.5 | 78.5 | 0 | New Acceptor Site? |
4.7
|
8.8
| -1.18661 | 6.7 | -0.04 | C0 | Tolerated | good | benign | polymorphism |
24447 | chr22:29130636 A>G |
CHEK2
| 2 | c.74T>C | p.V25A | 80 | 3’ | 1.7 | 1.7 | 0 | 85.5 | 85.5 | 0 | - | - | -0.166788 | 36.67 | -0.07 | C0 | Tolerated | good | benign | polymorphism | |
11705 | chr11:108160467 G>A |
ATM
| 29 | c.4375G>A | p.G1459R | -62 | 5’ | 8.9 | 8.9 | 0 | 87.5 | 87.5 | 0 | - | - | 0.552026 | -27.26 | -0.09 | C15 | Deleterious | bad | probably damaging | disease causing | |
chr2:47672694 C>G |
MSH2
| 8 | c.1284C>G | p.H428Q | 8 | 3’ | 10.1 | 10.1 | 0 | 87.3 | 87.3 | 0 | - | - | 0.703136 | 22.05 | 0.05 | C0 | Tolerated | good | possibly damaging | disease causing | ||
13393 & 25167 | chr:8_90983460 G>A |
NBN
| 6 | c.643C>T | p.R215W | 59 | 3’ | 6.2 | 6.2 | 0 | 86.8 | 86.8 | 0 | - | - | -1.00071 | -16.87 | -0.09 | C0 | Tolerated | good | probably damaging | polymorphism | |
14963 | chr16:23647635 C>T |
PALB2
| 4** | c.232G>A | p.V78I | 21 | 3’ | 10.0 | 10.0 | 0 | 90.3 | 90.3 | 0 | - | - | -0.783039 | -29.17 | 0.8 | C0 | Tolerated | good | benign | polymorphism | |
22953 | chr19:15278214 C>G |
NOTCH3
| 29 | c.5208G>C | p.E1736D | 9 | 3’ | 7.8 | 7.8 | 0 | 84.2 | 84.2 | 0 | - | - | 0.0501789 | -10.44 | 0.22 | C35 | Deleterious | bad | benign | disease causing | |
chr2:47630458 A>G |
MSH2
| 1* | c.128A>G | p.Y43C | -84 | 5’ | 10.1 | 10.1 | 0 | 90.6 | 90.6 | 0 | New Donor Site? | 0 | 1.2 | 1.50425 | 4.7 | 2.11 |
C55
| Deleterious | bad | probably damaging | disease causing | |
chr14:68352648 T>G |
RAD51B
| 6 | c.515T>G | p.L172W | -58 | 5’ | 9.5 | 9.5 | 0 | 83.7 | 83.7 | 0 | - | - | 1.62772 | 67.77 | 1.31 | C0 | Deleterious | bad | possibly damaging | polymorphism | ||
24789 | chr5:112175625 C>T |
APC
| 15* | c.4334C>T | p.T1445I | 2376 | 3’ | 7.5 | 7.5 | 0 | 93.6 | 93.6 | 0 | - | - | -1.61023 | -90.13 | - | C0 | Tolerated | good | benign | polymorphism | |
chr16:23646617 G>T |
PALB2
| 4** | c.1250C>A | p.S417Y | -435 | 5’ | 8.9 | 8.9 | 0 | 87.5 | 87.5 | 0 | - | - | -0.551724 | -22.83 | 0.05 | C0 | Deleterious | bad | probably damaging | disease causing | ||
8913 | chr2:47601029 G>C |
EPCAM
| 3 | c.267G>C | p.Q89H | 83 | 3’ | 7.0 | 7.0 | 0 | 90.1 | 90.1 | 0 | - | - | -0.40237 | -28.93 | 0 | C0 | Tolerated | bad | possibly damaging | disease causing |