Leveraging variant type to infer direction of effect, our observation that the QV model most significantly associated with prostate cancer risk and severity in BRCA2 and ATM was the ‘ptv model’ (containing only PTVs), suggests that these genes operate via a loss-of-function mechanism in prostate cancer (Table 2, Supplementary Data 1). This evidence concerns the gene BRCA2 and prostate carcinoma.