For example, Brca1 and Brca2 are tolerant of variation, ranking among the 9% ad 8% least constrained mouse genes; however, their human orthologues BRCA1 and BRCA2 contain high numbers of pathogenic variants that are causally linked to adult-onset hereditary cancer (Fig. 2A) [27, 28]. This evidence concerns the gene BRCA2 and hereditary cancer.