MRC1 and Lynch syndrome: For example, it is recognized that pathogenic PMS2 variants are less penetrant than other MMR gene variants in the context of Lynch syndrome (Møller et al., 2017; Ten Broeke et al., 2018), yet approximately 8% of CRCs in carriers of pathogenic PMS2 variants are diagnosed before the age of 30 and in the distal colon, much earlier than the mean onset at 48 years in probands and distinct from the proximal location that is typical of Lynch syndrome (Goodenberger et al., 2016).