This would partly account for the overall fewer (n = 45) PMS2 index cases detected as compared with the other MMR genes; however, a greater contribution to these lower numbers is likely to arise from the relatively low penetrance of PMS2 (no increased cancer risk at <50 years of age in prospective studies of Lynch Syndrome) [17], despite PMS2 variants being more common than for the other individual MMR genes [18] and further evidenced by the greater contribution to constitutional MMR deficiency [19]. This evidence concerns the gene PMS2 and cancer.