CHEK2 and breast cancer: Here, we comprehensively assess the impact of germline genetic variation on risk of breast cancer and show (1) how a high breast cancer PRS compares to high-risk mutations in breast cancer susceptibility genes, (2) how the PRS modifies the risk of breast cancer in women carrying pathogenic mutations in the PALB2 and CHEK2 genes and (3) that the PRS has utility for informing about risk of contralateral breast cancer, and about the risk in first-degree relatives.