Table 2.
Odds ratios (OR) and 95% confidence intervals (CI) for pathogenicity of missense variants in BRCA1 and BRCA2.
| Gene | Region | Codons | OR (95% CI)a | Bayesian analysis |
|---|---|---|---|---|
| BRCA1 | Ring domain | 9–98 | 8.4 (6.4–11.2) | Supports pathogenic |
| Exon 11 | 224–1366 | <0.01 (0.0–0.01) | Strong benign (coldspot) | |
| Coiled-coil domain | 1393–1424 | 0.6 (0.04–9.7) | Moderate benign | |
| BRCT repeats | 1649–1859 | 2.7 (0.9–8.6) | Supports pathogenic | |
| BRCA2 | exon 10 and 11 | 266–2281 | <0.01 (0.0–0.01) | Strong benign (coldspot) |
| DNA-binding domain | 2481–3186 | 1.0 (0.06–15.6) | Not informative |
aOdds ratios are calculated as (P + LP + 1/2)/(B + LB + 1/2). For example, an odds ratio of 1.0 indicates the same number of P + LP and B + LB variants in a given region. Based on Bayesian analysis (Tavtigian et al.18), odds ratios <0.48 were considered "supporting benign," <0.23 "moderate benign,” and <0.05 "strong benign.”