Together, our study suggests BRCA1, BRCA2, PALB2, RAD51C, BARD1, and RAD51D biallelic inactivation as the major genetic basis of human HRD, and it provides a novel opportunity for the precision medicine approaches in HRD and expands the population of patients who may benefit from agents targeting HRD. Here, BRCA2 is linked to hypoparathyroidism-retardation-dysmorphism syndrome.