Additional Table 3. BRCA2 variants.
| Exon | HGVS Nucleotide | HGVS Protein | Protein Abbrev | Other names | Type | Localization (GRCh37) | NCBI 1000 Genomes Browser | Global MAF dbSNP | Allele Frequency ExAC | Global MAF 1000 genomes | ESP | gnomAD | TOPMed | ABraOM | SIFT | PolyPhen | Provean | Align-GVGD (Pufferfish) | Human Splicing Finder | BRCA Exchange | BRCA Mutation Database | BRCA Share™ | ClinVar | Interpretation | n |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2 | c.-26G>A | - | - | 203G>A | 5'UTR | 13: 32890572 | rs1799943 | 0.20927 (A) | 0,24652 | 0,20927 | 0,20883 | 0,22032 | 0,21567 | 0.217570 | - | - | - | - | ND | Benign / Little Clinical Significance | ND | ND | Benign | Benign | 21 |
| 2 | c.-15A>C | - | - | 214A>C | 5'UTR | 13: 32890583 | rs138705202 | 0.00080 (C) | 0.00022 | 0,0008 | 0,00038 | 0,00064 | 0,00076 | 0.002463 | - | - | - | - | ND | Not Yet Reviewed | ND | ND | Benign/ Likely Benign | Likely benign | 1 |
| 2 | c.-11C>T | - | - | 218C>T | 5'UTR | 13: 32890587 | rs76874770 | 0.00439 (T) | 0,00163 | 0,00439 | 0,00584 | 0,0051 | 0,00546 | 0.007389 | - | - | - | - | ND | Benign / Little Clinical Significance | ND | ND | Benign | Benign | 2 |
| 2 | c.2T>G | p.Met1Arg | M1R | - | M | 13: 32890599 | rs80358547 | - | 0,00001 | - | - | 0,00001 | - | - | Damaging (0.00) | Probably Damaging (0.998) | Deleterious | Class C65 | ND | Not Yet Reviewed | 5-Definitely pathogenic | 5-Causal | Pathogenic? | Pathogenic | 1 |
| 3 | c.125A>G | p.Tyr42Cys | Y42C | 353A>G | M | 13: 32893271 | rs4987046 | 0.00080 (G) | 0,0017 | 0,0008 | 0,00246 | 0,00162 | 0,00158 | 0.001642 | Tolerate (0.12) | Benign (0.090) | Neutral | Class C0 | Activation of an exonic cryptic donor site. Potential alteration of splicing. | Benign / Little Clinical Significance | 1-Not pathogenic or of no clinical significance | 1-Neutral | Benign | Benign | 1 |
| 4 | c.425+33A>G | - | - | IVS4+33A>C | IVS | 13: 32899354 | rs200065709 | 0.00060 (G) | 0,00052 | 0,0006 | 0,00031 | 0.00010 | 0,00029 | 0.000821 | - | - | - | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Not Yet Reviewed | ND | 2-Likely Neutral | Benign/ Likely Benign | Likely benign | 1 |
| 4 | c.425+67A>C | - | - | IVS4+67A>C | IVS | 13: 32899388 | rs11571610 | 0.07428 (C) | - | 0,07428 | - | 0,03064 | 0,03973 | 0.045156 | - | - | - | - | Alteration of an intronic ESS site. Probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 6 |
| 6 | c.517-19C>T | - | - | IVS6-19C>T | IVS | 13: 32900617 | rs11571623 | 0.00819 (T) | 0,00219 | 0,00819 | 0,00738 | 0,00586 | 0,007 | 0.003284 | - | - | - | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 2 |
| 8 | c.681+56C>T | - | - | IVS8+56C>T | IVS | 13: 32903685 | rs2126042 | 0.18590 (T) | - | 0,1859 | - | 0,21627 | 0,20076 | 0.184729 | - | - | - | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Not Yet Reviewed | ND | 1-Neutral | Benign | Benign | 17 |
| 10 | c.865A>C | p.Asn289His | N289H | 1093A>C | M | 13: 32906480 | rs766173 | 0.07368 (C) | - | 0,07368 | 0,03055 | 0,03055 | 0,03968 | 0.045156 | Damaging (0.003) | Benign (0.278) | Neutral | Class C0 | Alteration of an exonic ESE site. Potential alteration of splicing | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 7 |
| 10 | c.1114A>C | p.His372Asn | H372N | 1342 A>C | M | 13: 32906729 | rs144848 | 0.24940 (C) | 0,27793 | 0,2494 | - | 0,22303 | 0,23657 | 0.259442 | Tolerated (0.35) | Benign (0.00) | Neutral | Class C0 | Alteration of an exonic ESE site. | Benign / Little Clinical Significance | 1-Not pathogenic or of no clinical significance | 1-Neutral | Benign | Benign | 19 |
| 10 | c.1365A>G | p.Ser455= | S455= | 1593A>G | Syn | 13: 32906980 | rs1801439 | 0.07368 (G) | 0,05178 | 7368 | 0,03101 | 0,03048 | 0,03968 | 0.045156 | - | - | Neutral | - | Alteration of an exonic ESE site. Potential alteration of splicing | ND | ND | 1-Neutral | Benign | Benign | 7 |
| 10 | c.1514T>C | p.Ile505Thr | I505T | M | 13: 32907129 | rs28897708 | 0.00040 (C) | 0,00072 | 0,0004 | 0,00077 | 0,00083 | 0,00065 | 0.000821 | Tolerated (0.1) | Possibly Damaging (0.651) | Neutral | Class C0 | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | 1-Not pathogenic or of no clinical significance | 1-Neutral | Benign | Benign | 1 | |
| 10 | c.1909+92_1909+96del | - | - | IVS10+92del5 | IVS | 13: 32907615-32907620 | rs144549870 | 0.01577 (TAT) | - | - | - | - | - | 0.006568 | - | - | - | - | - | ND | ND | ND | Benign | Benign | 2 |
| 10 | c.1910-74T>C | - | - | IVS10-74T>C | IVS | 13: 32910328 | rs2320236 | 0.17452 (C) | - | 0,17452 | - | 0,20561 | 0,20561 | rs2320236 | - | - | - | - | Creation of an intronic ESE site. Probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 14 |
| 10 | c.1910-51G>T | - | - | IVS10-51G>T | IVS | 13: 32910351 | rs11571651 | 0.07348 (T) | 0,04934 | 0,07348 | 0,03056 | 0,03041 | 0,03968 | 0.045977 | - | - | - | - | Alteration of an intronic ESS site. Probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 6 |
| 11 | c.2229T>C | p.His743= | H743= | 2457T>C | Syn | 13: 32910721 | rs1801499 | 0.07348 (C) | 0,05158 | 0.07348 | 0,03129 | 0,03065 | 0,03972 | 0.045156 | - | - | Neutral | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 7 |
| 11 | c.2350A>G | p.Met784Val | M784V | 2578A>G | M | 13: 32910842 | rs11571653 | 0.00359 (G) | 0,00031 | 0,00359 | - | 0,00023 | 0,00022 | 0.002463 | Tolerated (1.00) | Benign (0.00) | Neutral | Class C0 | Creation of an exonic ESS site. Potential alteration of splicing. | Benign / Little Clinical Significance | 3-Uncertain | 3-UV | Benign | Benign | 1 |
| 11 | c.2971A>G | p.Asn991Asp | N991D | 3199A>G | M | 13: 32911463 | rs1799944 | 0.08007 (G) | 0,05341 | 0,08007 | 0,03725 | 0,03723 | 0,0461 | 0.046798 | Tolerated (1.00) | Benign (0.00) | Neutral | Class C0 | Alteration of an exonic ESE site. Potential alteration of splicing | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 7 |
| 11 | c.3264T>C | p.Pro1088= | P1088= | 3492T>C | Syn | 13: 32911756 | rs36060526 | 0.00679 (C) | 0.00238 | 0,00679 | 0,00756 | 0,00762 | 0,00756 | 0.006568 | - | - | Neutral | - | ND | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 11 | c.3371A>G | p.Gln1124Arg | Q1124R | M | 13: 32911863 | rs1555283204 | - | - | - | - | - | - | - | Damaging (0.01) | Probably Damaging (1.00) | Deleterious | Class C35 | Activation of an exonic cryptic donor site. Potential alteration of splicing. | Not Yet Reviewed | ND | ND | Uncertain significance | Uncertain significance | 1 | |
| 11 | c.3396A>G | p.Lys1132= | L1132= | 3624A>G | Syn | 13: 32911888 | rs1801406 | 0.26677 (G) | 0,29449 | 0,26677 | 0,27984 | 0,29762 | 0,28221 | 0.283251 | - | - | Neutral | - | Alteration of an exonic ESE site. Potential alteration of splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 23 |
| 11 | c.3807T>C | p.Val1269= | V1269= | 4035T>C | Syn | 13: 32912299 | rs543304 | 0.16813 (C) | 0,18985 | 0,16813 | 0,19111 | 0,18144 | 0,18622 | 0.187192 | - | - | Neutral | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 23 |
| 11 | c.4068G>A | p.Leu1356= | L1356= | 4296G>A | Syn | 13: 32912560 | rs28897724 | 0.00040 (A) | 0,00305 | 0,0004 | 0,00315 | 0.00245 | 0,00312 | 0.002463 | - | - | Neutral | - | ND | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 11 | c.4090A>C | p.Ile1364Leu | I1364L | 4318A>C | M | 13: 32912582 | rs56248502 | 0.00439 (C) | 0,00172 | 0,00439 | 0,00631 | 0,00577 | 0.006568 | Tolerated (0.76) | Benign (0.001) | Neutral | Class C0 | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 2 | |
| 11 | c.4258G>T | p.Asp1420Tyr | D1420Y | 4486G>T | M | 13: 32912750 | rs28897727 | 0.00399 (T) | 0,0068 | 0,00399 | 0,00396 | 0,00794 | 0,00425 | 0.001642 | Damaging (0.01) | Benign (0.030) | Deleterious | Class C15 | ND | Benign / Little Clinical Significance | 1-Not pathogenic or of no clinical significance | 1-Neutral | Benign | Benign | 1 |
| 11 | c.5418A>G | p.Glu1806= | E1806= | 5646A>G | Syn | 13: 32913910 | rs34351119 | 0.00679 (G) | 0,00233 | 0,00679 | 0,0083 | 0,00764 | 0,00785 | 0.006568 | - | - | Neutral | - | ND | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 11 | c.5640T>G | p.Asn1880Lys | N1880K | 5868T>G | M | 13: 32914132 | rs11571657 | 0.00220 (G) | 0,00076 | 0,0022 | 0,00315 | 0,00264 | 0,00294 | 0.000821 | Damaging (0.05) | Benign (0.167) | Neutral | Class C0 | Creation of an exonic ESS site. Potential alteration of splicing. | Benign / Little Clinical Significance | 2-Likely not pathogenic or of little clinical significance | 2-Likely Neutral | Benign/Likely Benign | Likely benign | 1 |
| 11 | c.5645C>A | p.Ser1882Ter | S1882X | 5873C>A | N | 13: 32914137 | rs80358785 | - | 0,00002 | - | - | 0,00002 | 0,00002 | - | - | - | - | - | Alteration of an exonic ESE site. Potential alteration of splicing. | Pathogenic | 5-Definitely pathogenic | 5-Causal | Pathogenic | Pathogenic | 1 |
| 11 | c.5744C>T | p.Thr1915Met | T1915M | 5972C>T | M | 13: 32914236 | rs4987117 | 0.00859 (T) | 0,02114 | 0,02114 | 0,02114 | 0.00859 (T) | 0,01744 | 0.017241 | Tolerated (0.13) | Benign (0.000) | Neutral | Class C0 | Creation of an exonic ESS site. Potential alteration of splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 2 |
| 11 | c.5768A>C | p.Asp1923Ala | D1923A | 5996A>C | M | 13: 32914260 | rs45491005 | 0.00020 (C) | - | 0,0002 | 0,0002 | 0.00054 | 0.00105 | - | Tolerated (0.29) | Benign (0.144) | Deleterious | Class C0 | Alteration of an exonic ESE site. Potential alteration of splicing. | Benign / Little Clinical Significance | 2-Likely not pathogenic or of little clinical significance | 2-Likely Neutral | Benign | Likely benign | 1 |
| 11 | c.6841+53delTATTCAGTAG | - | - | - | IVS | 13: 32915384-32915394 | - | - | - | - | - | - | - | - | - | - | - | - | Alteration of an intronic ESS site. Probably no impact on splicing. | ND | ND | ND | ND | Uncertain Significance | 1 |
| 11 | c.6841+80delTTAA | - | - | IVS11+80delTTAA | IVS | 13: 32915411-32915414 | rs11571661 | 0.26578 (AA) | - | - | - | - | - | 0.279605 | - | - | - | - | Creation of an intronic ESE site. Probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 7 |
| 14 | c.7017G>C | p.Lys2339Asn | K2339N | 7245 G>C | M | 13: 32929007 | rs45574331 | 0.00679 (C) | 0,00228 | 0,00679 | 0,00808 | 0,00764 | 0,00786 | 0.006568 | Damaging (0.01) | Benign (0.105) | Neutral | Class C0 | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 2-Likely Neutral | Benign | Benign | 1 |
| 14 | c.7242A>G | p.Ser2414= | S2114= | 7470A>G | Syn | 13: 32929232 | rs1799955 | 0.23263 (G) | - | 0,23263 | 0,21136 | - | 0,22464 | 0.238095 | - | - | Neutral | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 19 |
| 14 | c.7319A>G | p.His2440Arg | H2440R | 7547A>G | M | 13: 32929309 | rs4986860 | 0.01038 (G) | 0,00304 | 0,01038 | 0,01054 | 0,00946 | 0,00967 | 0.007389 | Tolerated (0.55) | Benign (0.002) | Neutral | Class C0 | ND | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 14 | c.7397T>C | p.Ala2466Val | A2466V | - | M | 13: 32929387 | rs169547 | 0.02416 (T) | 0,99372 | 0.97584 | 0,9777 | 0,97881 | 0,98191 | 0.983580 | Tolerated (0.98) | Possibly Damaging (0.793) | Neutral | Class C0 | ND | ND | ND | 1-Neutral | Benign | Benign | 50 |
| 14 | c.7435+53C>T | - | - | IVS14+53C>T | IVS | 13: 32929478 | rs11147489 | 0.07248 (T) | - | 0,07248 | - | 0,0301 | 0,03924 | - | - | - | - | - | Creation of an intronic ESE site. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 15 | c.7469T>C | p.Ile2490Thr | I2490T | 7697T>C | M | 13: 32930598 | rs11571707 | 0.01597 (C) | 0,01436 | 0.01597 | 0,00161 | 0,0035 | 0,00913 | 0.021346 | Tolerated (1.00) | Benign (0.010) | Neutral | Class C45 | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 17 | c.7806-14T>C | - | - | IVS16-14T>C | IVS | 13: 32936646 | rs9534262 | 0.46845 (T) | 0,52083 | 0,53155 | 0,52015 | 0,54679 | 0,53151 | 0.523810 | - | - | - | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 3-UV | Benign | Likely benign | 36 |
| 19 | c.8460A>C | p.Val2820= | V2820= | 8688A>C | Syn | 13: 32944667 | rs9590940 | 0.01438 (C) | 0,00368 | 0,01438 | 0,01299 | 0,01105 | 0,01219 | 0.006568 | - | - | Neutral | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 2 |
| 19 | c.8487+47C>T | - | - | IVS19+47C>T | IVS | 13: 32944741 | rs11571744 | 0.01617 (T) | - | 0,01617 | 0,01523 | - | 0,01481 | 0.006568 | - | - | - | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 3-UV | Benign | Benign | 3 |
| 20 | c.8632+132dup | - | - | c.IVS20+132insC | IVS | 13: 32945368-32945369 | rs201392123 | 0.00899 (CC) | - | 0.00899 | - | 0,00619 | 0,00754 | 0.002627 | - | - | - | - | ND | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 2 |
| 21 | c.8755-66T>C | - | - | IVS21-66T>C | IVS | 13: 32953388 | rs4942486 | 0.48842 (T) | - | 0,51158 | - | 0,52569 | 0,51037 | 0.508210 | - | - | - | - | Alteration of an intronic ESS site. Probably no impact on splicing. Creation of an intronic ESE site. Probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 38 |
| 22 | c.8851G>A | p.Ala2951Thr | A2951T | 9079G>A | M | 13: 32953550 | rs11571769 | 0.00998 (A) | 0,00785 | 0.00998 | 0,00438 | 0,00363 | 0,00721 | 0.013136 | Damaging (0.00) | Probably Damaging (1.00) | Neutral | Class C55 | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 22 | c.8942A>G | p.Glu2981Gly | E2981G | 9170A>G | M | 13: 32953641 | rs398122716 | - | 0,00001 | - | - | 0,00002 | 0,00001 | - | Tolerated (0.16) | Benign (0.030) | Neutral | Class C65 | ND | ND | ND | 3-UV | Conflicting interpretations of pathogenicity? Likely benign(1);Uncertain significance(3) | Uncertain significance | 1 |
| 23 | c.9038C>T | p.Thr3013Ile | T3013I | - | M | 13: 32953971 | rs28897755 | - | 0,00023 | - | 0,00046 | 0,00019 | 0,0002 | - | Tolerated (0.24) | Probably Damaging (0.875) | Neutral | Class C0 | ND | Benign / Little Clinical Significance | 1-Not pathogenic or of no clinical significance | 1-Neutral | Benign | Benign | 1 |
| 24 | c.9257-83G>A | - | - | IVS24-83G>A | IVS | 13: 32968743 | rs9595456 | 0.05052 (A) | - | 0,05052 | - | 0,04116 | 0.04575 | 0.022989 | - | - | - | - | Creation of an intronic ESE site. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 4 |
| 24 | c.9257-16T>C | - | - | IVS24-16T>C | IVS | 13: 32968810 | rs11571818 | 0.00439 (C) | 0,00439 | 0,00765 | 0,00592 | 0,00548 | 0,00548 | 0.004926 | - | - | - | - | No significant splicing motif alteration detected. This mutation has probably no impact on splicing. | ND | ND | 3-UV | Benign | Likely benign | 1 |
| 27 | c.9730G>A | p.Val3244Ile | V3244I | 9958 G>A | M | 13: 32972380 | rs11571831 | 0.00679 (A) | - | - | 0,0083 | 0,00767 | 0,00787 | - | Tolerated (0.49) | Benign (0.000) | Neutral | Class C0 | ND | Benign / Little Clinical Significance | ND | 2-Likely Neutral | Benign | Benign | 1 |
| 27 | c.9976A>T | p.Lys3326Ter | K3326X | 10204A>T | N | 13: 32972626 | rs11571833 | 0.00439 (T) | 0,00702 | 0,00439 | 0.00646 | 0,00544 | 0,00547 | 0.004926 | - | - | - | - | Creation of an exonic ESS site. Potential alteration of splicing. Alteration of an exonic ESE site. Potential alteration of splicing. | Benign / Little Clinical Significance | 2-Likely not pathogenic or of little clinical significance | 1-Neutral | Benign | Benign | 1 |
| 27 | c.10110G>A | p.Arg3370= | R3370= | - | Syn | 13: 32972760 | rs28897762 | 0.00080 (A) | 0,00147 | 0,0008 | 0,00215 | 0,0014 | 0,00131 | 0.000821 | - | - | Neutral | - | Alteration of an exonic ESE site. Potential alteration of splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 1 |
| 27 | c.10234A>G | p.Ile3412Val | I3412V | 10462 A>G | M | 13: 32972884 | rs1801426 | 0.04493 (G) | 0,02266 | 0,04493 | 0,03729 | 0,0369 | 0,04054 | 0.021346 | Tolerrated (0.34) | Benign (0.002) | Neutral | Class C0 | Alteration of an exonic ESE site. Potential alteration of splicing. | Benign / Little Clinical Significance | ND | 1-Neutral | Benign | Benign | 4 |
HGVS: Human Genome Variation Society; MAF: Minor allele frequency; EXAC: Exome Aggregation Consortium; ESP: NHLBI Exome Sequencing Project Exome Variant Server; gnomAD: The Genome Aggregation Database; TOPMed: Trans-Omics for Precision Medicine; ABraOM: Brazilian genomic variants; SIFT: Sorting Intolerant From Tolerant; PolyPhen: Polymorphism Phenotyping; Provean: Protein Variation Effect Analyzer; Align-GVGD: Class C0 (less probable to interfere with protein function), C15, C25, C35, C45, C55, C65 (more probable to interfere with protein function); Syn: Synonymous; IVS: Intervening sequence; M: Missense; SS: Splice site; ND: Not determined; n: Number of patients bearing the variant