CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Pathogenic variants in the CFTR gene are causative of classic cystic fibrosis (CF) as well as some nonclassic CF phenotypes. In 2001, CF became the first target of pan-ethnic universal carrier screening by molecular methods. The American College of Medical Genetics and Genomics (ACMG) recommended a core panel of 23 disease-causing variants as the minimal set to be included in pan-ethnic carrier screening of individuals with no family history of the disease, and these variants were usually assessed using targeted methods. The original recommendation also left open the option for laboratories to offer expanded CFTR variant panels; however, at the time, expanded CFTR variant panels were met with some controversy on the basis of the available technologies and the limited phenotypic knowledge of rare variants. Both of those aspects have now evolved, prompting this update of the ACMG technical standards for CFTR variant testing.