Table 2. Classification of BRCA1 and BRCA2 variants on the basis of multifactorial and splicing information.
| Variant | A-GVGD | A-GVGD prior probability | Segreg-ation | Tumor Patho-logy | Co-occurrence | Family History | Odds for Causality | Posterior Probability of Pathogenicity | IARC Class | Splicing class | |
| BRCA1 | c.122A>G(p.His41Arg) | C25 | 0.29 | 159.17 | 2.95 | – | – | 469.56 | 0.995 | Class 5 | – |
| c.2759T>C (p.Val920Ala) | C0 | 0.01 | 0.002 | – | – | – | 0.002 | 1.52×10−5 | Class 1 | – | |
| c.4484G>C(Arg1495Thr) | C0 | 0.01 | – | – | – | – | – | – | – | Class 5 | |
| c.4991T>C (p.Leu1664Pro) | C0 | 0.01 | 0.01 | – | 1.29 | 0.03 | 0.0003 | 3.89×10−6 | Class 1 | Class 1 | |
| BRCA2 | c.1354C>A (p.Leu452Ile) | C0 | 0.01 | 0.03 | – | – | – | 0.03 | 0.0003 | Class 1 | – |
| c.440A>G (p.Gln147Arg) | C0 | 0.01 | 1.38 | 1.20 | 1.07 | 0.78 | 1.37 | 0.014 | Class 2 | Class 1 | |
| c.1514T>C (p.Ile505Thr) | C0 | 0.01 | 0.16 | 1.20 | – | – | 0.191 | 0.002 | Class 2 | Class 1 | |
| c.4609G>A (p.Glu1537Lys) | C0 | 0.01 | 0.004 | – | – | – | 0.004 | 4.24×10−5 | Class 1 | – | |
| c.5070A>C (p.Lys1690Asn) | C0 | 0.01 | 0.48 | – | 0.30 | 3.23×10−5 | 4.55×10−6 | 4.59×10−8 | Class 1 | – | |
| c.5278T>G (p.Ser1760Ala) | C0 | 0.01 | 1.38 | 0.14 | – | – | 0.1977 | 0.002 | Class 2 | – | |
| c.5714A>G (p.His1905Arg) | C0 | 0.01 | 0.16 | – | – | – | 0.16 | 0.0016 | Class 2 | – | |
| c.6172T>A (p.Phe2058Ile) | C15 | 0.29 | 0.04 | – | 1.12 | 0.20 | 0.008 | 0.003 | Class 2 | – | |
| c.6322C>T (p.Arg2108Cys) | C0 | 0.01 | 0.06 | – | – | – | 0.06 | 0.0006 | Class 1 | – | |
| c.7521A>G (p. = ) | SYN | 0.01 | 0.01 | – | – | – | 0.01 | 9.89×10−5 | Class 1 | Class 1 | |
| c.7534C>T (p.Leu2512Phe) | C0 | 0.01 | 0.11 | – | – | – | 0.11 | 0.0011 | Class 2 | – | |
| c.7828G>A (p.Val2610Met) | C15 | 0.29 | 0.83 | – | – | – | 0.8288 | 0.25 | Class 3 | Class 1 | |
| c.8734G>A (p.Ala2912Thr) | C0 | 0.01 | 0.14 | – | – | – | 0.14 | 0.0014 | Class 2 | Class 1 | |
| c.9038C>T (p.Thr3013Ile) | C0 | 0.01 | 0.23 | – | – | – | 0.23 | 0.002 | Class 2 | – | |
| c.9364G>A (p.Ala3122Thr) | C0 | 0.01 | 0.34 | – | – | – | 0.34 | 0.0034 | Class 2 | – | |
Classifications for multifactorial likelihood as described in Plon et al. (3) and splicing as described in Spurdle et al. (32). Frequency data from 1000 Genomes and EVS datasets is available for a subset of the variants studied (Table S2). Information used to determine tumor pathology LRs was as follows: BRCA1c.122A>G(p.His41Arg) - one ER-positive Grade 3 tumor; BRCA2 variants c.440A>G (p.Gln147Arg) and c.1514T>C (p.Ile505Thr) - tubule formation present in <10% of tumor; BRCA2:c.5278T>G (p.Ser1760Ala) – tubule formation in >75% tumor.