ClinVar

Description

The CFTR c.2175dup; p.Glu726ArgfsTer4 variant (rs746418935) is reported in the literature in individuals affected with cystic fibrosis (Smit 1993, Sosnay 2013, Sugarman 2004). This variant is reported in ClinVar (Variation ID: 7185) and is found in the African population with an allele frequency of 0.03% (8/24,954 alleles) in the Genome Aggregation Database. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Furthermore, in vitro functional assays show a significant reduction in transcript expression (Smit 1993). Based on available information, this variant is considered to be pathogenic. References: Smit LS et al. An African-American cystic fibrosis patient homozygous for a novel frameshift mutation associated with reduced CFTR mRNA levels. Hum Mutat. 1993;2(2):148-51. PMID: 7686423. Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013 Oct;45(10):1160-7. PMID: 23974870. Sugarman EA et al. CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. Genet Med. 2004 Sep-Oct;6(5):392-9. PMID: 15371903.