Rare, protein-truncating variants in <i>ATM</i>, <i>CHEK2</i> and <i>PALB2</i>, but not <i>XRCC2</i>, are associated with increased breast cancer risks.

BACKGROUND: Breast cancer (BC) is the most common malignancy in women and has a major heritable component. The risks associated with most rare susceptibility variants are not well estimated. To better characterise the contribution of variants in METHODS: Gene coding regions were enriched via PCR, sequenced, variant called and filtered for quality. ORs for BC risk were estimated separately for carriers of truncating variants and of rare missense variants, which were further subdivided by functional domain and pathogenicity as predicted by four RESULTS: Truncating variants in CONCLUSIONS: Truncating variants in