Table 2.
Characterization of germline variants found among Norwegian familial CRC individuals
| 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 |
a Recently classified as Benign by ACMG Guidelines, 2015
b Patient ID carrying CHEK2 c.470 T > C, p.I157T