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

Joshua L Deignan; Caroline Astbury; Garry R Cutting; Daniela Del Gaudio; Anthony R Gregg; Wayne W Grody; Kristin G Monaghan; Sue Richards; ACMG Laboratory Quality Assurance Committee

doi:10.1038/s41436-020-0822-5

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

Genet Med. 2020 Aug;22(8):1288-1295. doi: 10.1038/s41436-020-0822-5. Epub 2020 May 14.

Authors

Joshua L Deignan¹, Caroline Astbury², Garry R Cutting³, Daniela Del Gaudio⁴, Anthony R Gregg⁵, Wayne W Grody⁶, Kristin G Monaghan⁷, Sue Richards⁸; ACMG Laboratory Quality Assurance Committee

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
³ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Human Genetics, The University of Chicago, Chicago, IL, USA.
⁵ Department of Obstetrics and Gynecology, Baylor University Medical Center, Dallas, TX, USA.
⁶ Departments of Pathology and Laboratory Medicine, Pediatrics, and Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ GeneDx, Gaithersburg, MD, USA.
⁸ Department of Molecular and Medical Genetics, Knight Diagnostic Laboratories, Oregon Health & Science University, Portland, OR, USA.

Abstract

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.

Keywords: fibrosis; genome; pancreatitis; screening; variant.

MeSH terms

Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
Genetic Testing / standards*
Genetics, Medical*
Genomics
Humans
Mutation
United States

Substances

CFTR protein, human
Cystic Fibrosis Transmembrane Conductance Regulator

Grants and funding

R01 DK044003/DK/NIDDK NIH HHS/United States