Table A2.
BRCA1 and BRCA2 Breast Tumor Characteristics
| Sequence Change | Sample | Race | Conserved Domain | A-GVGD Class | LOH | Splice Defect | In Trans | Age at Diagnosis (years) | Grade | ER Status | PR Status | HER-2 Status | Histology |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BRCA1 truncating | |||||||||||||
| 1135insA | 1463 | White | NA | NA | WT | ND | NA | 38 | 3 | − | − | − | IDC |
| 1240delC | 0409 | White | NA | NA | WT | ND | NA | 38 | 2 | − | − | − | DCIS |
| 1294del40 | 4439 | White | NA | NA | WT | ND | NA | ND | 4 | − | − | ND | IDC |
| 1294del40 | 127345 | White | NA | NA | WT | ND | NA | 40 | 3 | − | − | + | IDC |
| 1294del40 | 78081 | White | NA | NA | WT | ND | NA | 51 | 1 | − | − | ND | IDC |
| 1294del40 | 169184 | White | NA | NA | WT | ND | NA | 32 | ND | − | − | − | ND |
| 1547del10 | 21538 | White | NA | NA | WT | ND | NA | 33 | 3 | − | − | + | IDC |
| 1623del5 | 71759 | White | NA | NA | WT | ND | NA | 39 | 2 | − | − | + | IDC |
| 1675delA | 10950 | White | NA | NA | WT | ND | NA | 36 | 3 | − | − | ND | IDC |
| 1793delA | 12313 | Hispanic | NA | NA | WT | ND | NA | 37 | 3 | − | − | − | IDC |
| 187delAG | 45251a* | Ash J | NA | NA | WT | ND | NA | 35 | 3 | − | − | + | IDC |
| 187delAG | 45251b* | Ash J | NA | NA | WT | ND | NA | 36 | 3 | − | − | − | IDC |
| 187delAG | 5042 | Ash J | NA | NA | WT | ND | NA | 35 | 3 | − | − | − | IDC |
| 2530delAG | 458 | White | NA | NA | WT | ND | NA | 30 | 2 | − | − | − | IDC |
| 2553delC | 4724 | Hispanic | NA | NA | WT | ND | NA | 27 | 3 | − | ND | ND | IDC |
| 2576delC | 61933 | White | NA | NA | WT | ND | NA | 58 | 3 | − | − | − | IDC |
| 2576delC | 175158 | White | NA | NA | WT | ND | NA | 47 | ND | + | + | − | IDC |
| 2800delAA | 24042a* | White | NA | NA | WT | ND | NA | 39 | 3 | ND | ND | ND | IDC |
| 2800delAA | 24042b* | White | NA | NA | None | ND | NA | 47 | 2 | − | − | − | IDC |
| 3118delA | 11984 | Hispanic | NA | NA | V | ND | NA | 32 | 3 | − | − | − | IDC |
| 3600del11 | 34406 | White | NA | NA | WT | ND | NA | 37 | 2 | − | − | − | Unspecified |
| 5382insC | 20758 | Ash J | NA | NA | WT | ND | NA | 61 | 2 | − | − | ND | IDC |
| E143X | 34642 | White | NA | NA | WT | ND | NA | 32 | 3 | − | − | − | IDC |
| Q563X | 61051 | White | NA | NA | WT | ND | NA | 47 | 3 | + | − | − | IDC |
| S868X | 176811 | White | NA | NA | None | ND | NA | 74 | 3 | + | + | − | ILC |
| Q1408X | 34642 | White | NA | NA | None | ND | NA | 29 | ND | − | − | − | Unspecified |
| BRCA1 splice defect | |||||||||||||
| IVS4-1 G>T | 2364a* | White | NA | NA | WT | Yes† | No | 48 | 3 | − | − | ND | DCIS, LCIS |
| IVS4-1 G>T | 2364b* | White | NA | NA | WT | Yes† | No | 49 | 1 | + | + | − | DCIS, LCIS |
| IVS13+1 G>A | 98453 | White | NA | NA | None | Yes‡ | No | 41 | 2 | − | − | − | IDC |
| IVS15+1 G>A | 2-112-140 | White | NA | NA | WT | Yes‡ | No | ND | 4 | − | − | ND | IDC |
| IVS5-11 T>G | 45949 | White | NA | NA | WT | Yes | No | 59 | 2 | − | − | − | Medullary |
| BRCA1 intronic | |||||||||||||
| IVS12+1 0G>C | 78081 | White | NA | NA | None | ND | No | 51 | 1 | − | − | ND | IDC |
| IVS20-14 C>G | 168788 | White | NA | NA | None | No | No | 34 | 3 | + | + | − | IDC |
| IVS2-14 C>T | 64703 | White | NA | NA | V | No | No | 44 | 1 | + | + | − | IDC |
| IVS2-6 T>C | 15007 | White | NA | NA | None | ND | No | 38 | ND | + | + | − | DCIS |
| BRCA1 missense | |||||||||||||
| C61G | 14068 | White | Yes | C65 | WT | ND | No | 32 | 3 | − | − | + | IDC |
| C61G | 19882 | White | Yes | C65 | WT | ND | No | 29 | 3 | − | − | − | IDC |
| E597K | 98286 | White | No | C0 | None | ND | No | 45 | 1 | + | + | ND | IDC |
| E736A | 15102 | Asian | No | C0 | None | ND | No | 44 | ND | + | + | − | DCIS |
| I1275V | 4061 | White | No | C0 | WT | ND | No | 37 | 3 | − | − | − | IDC |
| K1109N | 0477a* | White | No | C0 | None | ND | No | 35 | ND | ND | ND | ND | DCIS |
| K1109N | 0477b* | White | No | C0 | None | ND | No | 49 | 2 | + | + | − | IDC |
| L1764P | 4744 | White | Yes | C35 | WT | ND | No | 32 | 3 | − | − | + | IDC |
| P1637L | 175158 | White | Close | C0 | WT | ND | No | 47 | ND | + | + | − | IDC |
| P1776H | 154045 | White | No | C0 | WT | ND | No | 48 | 3 | + | + | − | ND |
| P1776H | 133886 | White | No | C0 | WT | ND | No | 55 | ND | ND | ND | ND | Unspecified |
| P334H | 34402 | White | No | C0 | None | ND | No | 38 | 2 | + | + | − | IDC |
| S127N | 4060 | Af Am/N Am | No | C0 | V | ND | No | 38 | ND | ND | ND | ND | IDC |
| V1247I | 11092 | Asian | No | C0 | None | ND | No | 40 | 3 | + | + | − | IDC |
| V1804D | 16719 | White | Yes | C0 | V | ND | No | 58 | 2 | + | − | + | IDC |
| V1804D | 73481 | White | Yes | C0 | ND | ND | No | 59 | 1 | + | + | ND | IDC |
| V772A | 78081 | White | No | C0 | WT | ND | Yes | 47 | 1 | − | − | ND | IDC |
| T1310K | 176831 | White | No | C0 | None | ND | No | 45 | ND | ND | ND | ND | DCIS |
| Y856H | 1995 | Asian | No | C0 | None | ND | Yes | 45 | 3 | + | + | + | DCIS |
| Y856H | 4294 | Asian | No | C0 | None | ND | Yes | 47 | ND | ND | ND | ND | DCIS |
| BRCA2 truncating | |||||||||||||
| 2041delA | 46662 | White | NA | NA | None | ND | NA | 34 | 3 | + | + | − | IDC |
| 3036del4 | 4208 | White | NA | NA | U | ND | NA | ND | 2 | + | + | − | IDC |
| 3036del4 | 4310 | Asian | NA | NA | WT | ND | NA | 36 | 3 | + | + | + | IDC |
| 3036del4 | 542 | White | NA | NA | WT | ND | NA | 43 | ND | + | + | ND | IDC |
| 3972del4 | 5-077 | White | NA | NA | WT | ND | NA | ND | ND | + | + | ND | IDC |
| 4206ins4 | 26949 | White | NA | NA | None | ND | NA | 37 | 1 | + | + | − | LCIS |
| 4361del4 | 2609 | White | NA | NA | WT | ND | NA | ND | ND | − | + | − | IDC |
| 5270delTG | 169989 | White | NA | NA | None | ND | NA | 46 | 2 | + | − | ND | IDC |
| 6174delT | 4317 | Ash J | NA | NA | WT | ND | NA | 46 | 3 | − | − | − | IDC |
| 6503delTT | 35962 | White | NA | NA | WT | ND | NA | 46 | 2 | + | + | + | IDC |
| 7990del3ins2 | 15494 | White | NA | NA | WT | ND | NA | 41 | 3 | + | − | − | IDC |
| 8765delAG | 5702 | White | NA | NA | ND | ND | NA | 50 | ND | − | − | ND | IDC |
| 8803delC | 80659 | White | NA | NA | None | ND | NA | 36 | ND | + | + | ND | Unspecified |
| 9481insA | 94467 | White | NA | NA | WT | ND | NA | 64 | 2 | + | + | + | IDC |
| Q321X | 3-744 | White | NA | NA | V | ND | NA | ND | 4 | + | + | − | IDC |
| S1882X | 3553 | Asian | NA | NA | WT | ND | NA | 37 | 3 | + | + | − | IDC |
| Y1894X | 11008 | White | NA | NA | WT | ND | NA | 26 | ND | + | + | − | IDC |
| BRCA2 intronic | |||||||||||||
| IVS13+5 G>C | 16004 | White | NA | NA | WT | ND | No | 46 | 2 | + | + | − | IDC |
| IVS23+9 C>T | 12673 | White | NA | NA | WT | No | No | 40 | 2 | + | + | + | IDC |
| IVS8-12delTA | 64703 | White | NA | NA | None | No | No | 44 | 1 | + | + | − | IDC |
| BRCA2 missense | |||||||||||||
| A1170V | 143226 | White | No | C0 | ND | ND | No | 52 | 3 | − | + | + | IDC |
| A2351G | 2664 | Asian | No | C0 | None | ND | No | 61 | 3 | − | − | − | IDC |
| D1352Y | 11193 | White | No | C0 | WT | ND | No | 47 | 2 | + | + | − | IDC |
| E2856A | 5047 | White | Yes | C0 | V | ND | No | 45 | 2 | + | + | − | IDC |
| H1966Y | 46345 | White | No | C0 | V | ND | No | 44 | 3 | − | − | − | IDC |
| I2285V | 4112 | White | No | C25 | V | ND | No | ND | 2 | + | + | + | IDC |
| K1434I | 34415 | White | No | C15 | None | ND | No | 58 | ND | + | − | ND | DCIS |
| L2106P | 161491 | White | No | C0 | None | ND | No | 57 | 3 | + | + | − | IDC |
| L929S | 14388 | Af Am | No | C0 | None | ND | Yes | 37 | 2 | + | + | − | IDC |
| M2676T | 565 | White | Yes | C0 | None | ND | No | 49 | ND | + | ND | ND | IDC |
| N1878K | 14573a* | White | No | C0 | V | ND | No | 63 | 1 | + | − | − | IDC |
| N1878K | 14573b* | White | No | C0 | V | ND | No | 67 | 2 | + | + | − | IDC |
| N517S | 11859 | White | No | C0 | None | ND | No | 45 | 1 | + | + | ND | IDC |
| N588D | 0772 | White | No | C0 | WT | ND | No | 56 | 2 | + | + | + | IDC |
| N987I | 14388 | Af Am | No | C0 | None | ND | Yes | 37 | 2 | + | + | − | IDC |
| P1819S | 4146 | White | No | C0 | None | ND | No | 57 | 1 | + | + | − | IDC |
| P655R | 11631 | Ash J | No | C0 | None | ND | No | 38 | 3 | + | + | − | IDC |
| R2034C | 2098 | White | No | C0 | None | ND | Yes | 75 | 3 | − | − | + | IDC |
| R2418G | 26664 | White | Yes | C0 | None | ND | No | 61 | 2 | + | + | − | IDC |
| R2502H | 98245 | White | Yes | C0 | None | ND | No | 58 | 3 | + | + | − | IDC |
| R2973C | 2382 | White | Yes | C25 | WT | ND | No | 52 | 2 | + | + | − | IDC |
| S1424C | 155088 | White | No | C0 | None | ND | No | 55 | ND | ND | ND | ND | ND |
| S2483N | 25006 | White | Yes | C0 | None | ND | No | 48 | 1 | + | + | − | IDC |
| S384F | 6996 | White | No | C0 | WT | ND | Yes | 49 | 2 | + | + | + | IDC |
| T2681R | 25705 | White | Yes | C0 | WT | ND | No | 34 | 3 | − | − | − | IDC |
| T3211K | 59457 | White | Yes | C0 | None | ND | No | 52 | 3 | − | − | − | ND |
| Y42C | 4620 | White | No | C0 | V | ND | No | 40 | ND | − | − | − | IDC |
Abbreviations: A-GVGD, align grantham variation deviation analysis; LOH, loss of heterozygosity; ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2; NA, not applicable; WT, loss of wild-type allele; ND, no data; −, negative; IDC, invasive ductal carcinoma; DCIS, ductal carcinoma in situ; +, positive; Ash J, Ashkenazi Jewish; V, loss of variant allele; ILC, invasive lobular carcinoma; LCIS, lobular carcinoma in situ; Af Am, African American; N Am, Native American; U, uncertain loss.
*
Individual has bilateral breast cancer, and both tumors were included.
†
Change shown to affect splicing by others.
‡
Change predicted to affect splicing by SpliceSiteFinder.