Table 2.
Genes with rare variants associated with an increased breast cancer risk
| Gene | PTV associated with breast cancer risk | Missense variants associated with breast cancer risk | Relative risk for PTV (90% CI) | Clinical Genome Resource (ClinGen) definition of clinical relevance |
|---|---|---|---|---|
| ATM | Yes | Yes | 2.8 (2.2–3.7) | Definitive |
| BARD1 | Likely | Unknown | 2.1 (1.5–3.0)48 | Definitive |
| BRCA1 | Yes | Yes | 11.4 (NA) | Definitive |
| BRCA2 | Yes | Yes | 11.7 (NA) | Definitive |
| CDH1 | Yes | Unknown | 6.6 (2.2–19.9) | Definitive |
| CHEK2 | Yes | Yes | 3.0 (2.6–3.5) | Definitive |
| NBN | Yes | Unknown | 2.7 (1.9–3.7) | Limited |
| NF1 | Yes | Unknown | 2.6 (2.1–3.2) | Not evaluated |
| PALB2 | Yes | Unknown | 5.3 (3.0–9.4) | Definitive |
| PTEN | Yes | Yes | 8.8 (2.7–34.4)48 | Definitive |
| RAD51D | Likely | Unknown | 2.1 (1.2–3.72)48 | Limited |
| STK11 | Yes | Unknown | No reliable estimate | Definitive |
| TP53 | Yes | Yes | 105 (62–165) | Definitive |
Data were sourced from Easton et al.42 and Lee et al.57, with risk estimates derived from Easton et al.42, except where indicated otherwise. Note that risk estimates calculated by LaDuca et al.48 come with 95% confidence intervals (CIs) and are derived from a study of individuals referred for testing and, therefore, might not be unbiased estimates of the general population risk. NA, not available; PTV, protein-truncating variants.