Thirty-eight missense variants had an ExAC carrier frequency >0.1% (25/299 in ATM, 4/77 in CHEK2, 7/125 in PALB2 and 2/34 in XRCC2; see online supplementary table S4), and two were significantly associated with BC risk: ATM c.7390T>C (p.Cys2464Arg, rs55801750, OR(Arg/Cys)=0.37; 95% CI 0.19 to 0.73, Ptrend=0.0028) and XRCC2 c.563G>A (p.Arg188His, rs3218536, OR(His/Arg)=0.90; 95% CI 0.83 to 0.97, Ptrend=0.0080) (see online supplementary table S7). This evidence concerns the gene CHEK2 and breast cancer.