For example, a second hit rarely occurs in breast cancers from carriers of the lower penetrance CHEK2 p.(Ile157Thr) variant24 or the BRCA2 p.(Lys3326Ter) variant22, while limited reports suggest that it does occur in breast cancers from women carrying germline CHEK2 LoF variants24,25. The gene discussed is BRCA2; the disease is breast carcinoma.