Several other studies of missense VUSs in BRCA2 based on multifactorial likelihood classification models incorporating personal and family history of cancer, co-segregation of variants with disease, and in silico sequence-based prediction models have been published.14, 15, 16 These quantitative models, that do not incorporate protein functional data for variant classification are useful for comparisons with results from the ACMG/AMP rules-based approach reported here. The gene discussed is BRCA2; the disease is cancer.