Background: Data from Lynch syndrome (LS) registries reveal that patients (pts) with PMS2 pathogenic germline variants (PGVs) have the lowest cancer risk. This retrospective study of pts undergoing germline genetic testing (GGT) for any indication compared the phenotypes of PMS2 carriers to other LS pts. We hypothesized that PMS2 pts were more likely to have no cancer or non–LS associated cancers than other LS pts. Methods: All Pts with a single PGV in any LS gene were identified from a commercial laboratory database. Demographics and personal and family cancer history data were clinician-reported on the test requisition form. Data from PMS2 pts were compared to MSH6 and MLH1/MSH2/EPCAM pts using descriptive statistics, unpaired two-samples t tests, Chi-square tests, and multivariate logistic regression analyses that also included patients with no PGVs, with p<0.05 defining significance. Results: 17,711 pts met inclusion criteria (5,189 PMS2, 5,182 MSH6, and 7,340 MLH1/MSH2/EPCAM). PMS2 pts were significantly older at testing (mean 55.1±16.0y) than MLH1/MSH2/EPCAM (48.7±15.7y) and had significantly less family cancer history (84.9%) than both MSH6 (86.8%) and MLH1/MSH2/EPCAM (86.6%) pts. PMS2 pts had lower odds of any colorectal and uterine cancers than the MSH6 and MLH1/MSH2/EPCAM cohorts (Table). All LS-related PGVs were significantly associated with lower odds of breast, pancreatic, and prostate cancer. Conclusions: Pts with PMS2 PGVs were older at the time of testing and had lower odds of any and LS-related cancers than other LS pts. These data are consistent with prior registry studies and can aid in counseling and management of PMS2 pts.