Submissions for variant NM_000492.4(CFTR):c.2669A>G (p.Gln890Arg)

dbSNP: rs397508417

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000577280	SCV001532692	uncertain significance	Cystic fibrosis	2022-05-20	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 890 of the CFTR protein (p.Gln890Arg). This variant is present in population databases (rs397508417, gnomAD 0.0009%). This missense change has been observed in individual(s) with congenital unilateral absence of the vas deferens (CUAVD) (PMID: 10875853). ClinVar contains an entry for this variant (Variation ID: 53540). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001797613	SCV002041562	uncertain significance	not specified	2024-02-19	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.2669A>G (p.Gln890Arg) results in a conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251194 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2669A>G has been reported in the literature in at least one compound heterozygous individual affected with Cystic Fibrosis (Larriba_2001) and one patient affected with CAVD (Casals_2000). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 10875853, 11466205). ClinVar contains an entry for this variant (Variation ID: 53540). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV000577280	SCV002744857	uncertain significance	Cystic fibrosis	2022-01-24	criteria provided, single submitter	clinical testing	The p.Q890R variant (also known as c.2669A>G), located in coding exon 17 of the CFTR gene, results from an A to G substitution at nucleotide position 2669. The glutamine at codon 890 is replaced by arginine, an amino acid with highly similar properties. This alteration has been identified in multiple individuals with congenital absence of the vas deferens (Casals T et al. Hum Reprod, 2000 Jul;15:1476-83; Larriba S et al. Biol Reprod, 2001 Aug;65:394-400). Of note, this alteration is also known as 2801A>G in published literature. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002496713	SCV002777747	uncertain significance	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2022-02-16	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577280	SCV000679356	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV001831753	SCV002080790	uncertain significance	CFTR-related disorder	2019-10-09	no assertion criteria provided	clinical testing