ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.7526G>A (p.Arg2509Gln)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003079690 SCV003471203 uncertain significance not provided 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2509 of the USH2A protein (p.Arg2509Gln). This variant is present in population databases (rs781229974, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. 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 disruptive. This variant disrupts the p.Arg2509 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 28157192, 32188678, 32675063), which suggests that this may be a clinically significant amino acid residue. 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.
GeneDx RCV003079690 SCV003852943 uncertain significance not provided 2023-03-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV003455700 SCV004183238 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455699 SCV004183239 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003455700 SCV005044843 uncertain significance Retinitis pigmentosa 39 criteria provided, single submitter clinical testing The missense c.7526G>A p.Arg2509Gln variant in USH2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg2509Gln variant has allele frequency 0.002% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has not been reported to the ClinVar database. The amino acid change p.Arg2509Gln in USH2A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 2509 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance VUS.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.