This refined estimate is comparable to the prevalence of germline pathogenic DICER1 variants in The Cancer Genome Atlas (1 in 4600; n = 9173 exomes).16 It is also comparable to the prevalence of other common genetic disorders, such as fragile X,26 22q11.2 deletion syndrome,27 and neurofibromatosis type 1.28 The discovery, through genome-first approaches, that pathogenic variant prevalence in DICER1 (and in other important tumor-predisposition genes, such as BRCA1 and BRCA24) is more common than expected has important clinical implications. Here, DICER1 is linked to 22q11.2 deletion syndrome.