Criteria applicable include: population frequency data (absence in gnomADSV; PM2_supporting), variant type and location (proven in-frame duplication within domain; PVS1_Strong); lack of recessive Fanconi Anemia phenotype (no physical features, chromosome normal range, no chemotoxicity, cancer age 64y (> 50y); BS2); breast tumor features against pathogenicity (LR 0.32, for ER positive HER2 positive tumor; BP5_Supporting) according to [25]. The gene discussed is ESR1; the disease is neoplasm.