ClinVar

Description

The CFTR c.2173G>A; p.Glu725Lys variant (rs199791061) has been described in patients with cystic fibrosis, but without strong evidence for pathogenicity (des Georges 2004, Kanavakis 2003). This variant has also been reported in the heterozygous state in one individual with suboptimal fertility and one individual affected with hypertrypsinemia (Gene 2008, Larriba 2005). This variant is also reported in ClinVar (Variation ID: 53448). This variant is found in the general population with an overall allele frequency of 0.009% (28/282634 alleles) in the Genome Aggregation Database. The glutamic acid at codon 725 is moderately conserved, computational analyses predict that this variant is deleterious (REVEL: 0.77). However, given the lack of clinical and functional data, the significance of the p.Glu725Lys variant is uncertain at this time. References: Des Georges M et al. High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France. J Cyst Fibros. 2004 Dec;3(4):265-72. Gene G et al. N-terminal CFTR missense variants severely affect the behavior of the CFTR chloride channel. Hum Mutat. 2008 May;29(5):738-49. Kanavakis E et al. Cystic fibrosis in Greece: molecular diagnosis, haplotypes, prenatal diagnosis and carrier identification amongst high-risk individuals. Clin Genet. 2003 May;63(5):400-9. Larriba S et al. Molecular evaluation of CFTR sequence variants in male infertility of testicular origin. Int J Androl. 2005 Oct;28(5):284-90.