Taking into account the diversity and general high concordance of the in silico tools that were considered for the prediction of variant pathogenicity (S2 Table), along with the low frequency found among the 710 healthy control cases screened (S3 Table) and with the fact that other missense mutations in ATM, CHEK2 and TP53 have been linked with cancer development [61,62], it is plausible that the variants in ATM, BRIP1, CHEK2 and TP53 here identified may explain PrCa susceptibility in the families carrying them. Here, CHEK2 is linked to cancer.