CFTR Carrier Screening
June 9, 2023
Last Updated Month/Year
September 5, 2023
Country of Publication
Pathogenic variants in the CFTR gene are causative of cystic fibrosis (CF) as well as CF-related disorders, such as isolated congenital bilateral absence of the vas deferens (CBAVD). In 2001, several professional organizations joined in acknowledging the importance and technologic advances that would make CF amenable to population-based carrier screening. However, the technology and knowledge had not advanced far enough to allow for an equitable application. Variant databases were far less advanced when compared with those that are easily and widely accessible today. Sequencing technology was also early in development. This limited screening to small sets of variants that were most commonly characterized in Ashkenazi Jewish and Northern European populations using targeted, allele-specific testing approaches rather than DNA sequencing. For this reason, recommendations at that time were that screening should be “offered” to those of Ashkenazi Jewish and Northern European descent and “made available” to other groups, partly in recognition that the carrier frequencies are highest in those 2 ethnicities, but with the additional implication being that the identification of heterozygotes was not the same across all racial and/or ethnic groups (and indeed quite suboptimal in some). The American College of Medical Genetics and Genomics (ACMG) ultimately recommended a set of 25 pathogenic variants, later reduced to 23 pathogenic variants with an allele frequency of ≥0.1% in patients with CF in the US population to represent a minimum variant set for pan-ethnic carrier screening of individuals with no family history of CF. This minimum variant set (often referred to as the “ACMG-23”) has remained unchanged since then, even as molecular diagnostic technologies and genetic knowledge have dramatically advanced.
Male, Female, Adolescent, Adult
Health Care Settings
Ambulatory, Laboratory services
Genetics, nurse, nurse practitioner, physician, physician assistant
Assessment and screening
D003550 - Cystic Fibrosis
cystic fibrosis, pancreatitis, CFTR, cystic fibrosis (CF), carrier screening, genetic carrier screening
Deignan JL, Gregg AR, Grody WW, Guo MH, Kearney H, Monaghan KG, Raraigh KS, Taylor J, Zepeda-Mendoza CJ, Ziats C; ACMG Board of Directors. Electronic address: email@example.com. Updated recommendations for CFTR carrier screening: A position statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023 Jun 9:100867. doi: 10.1016/j.gim.2023.100867. Epub ahead of print. PMID: 37310422.