ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.15496A>G (p.Ile5166Val)

gnomAD frequency: 0.00006  dbSNP: rs111033419
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002513599 SCV005921362 uncertain significance not provided 2024-10-15 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32531858, 26969326, 27460420, 35266249)
Baylor Genetics RCV003460550 SCV004208215 uncertain significance Retinitis pigmentosa 39 2023-11-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002513599 SCV003522993 pathogenic not provided 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 5166 of the USH2A protein (p.Ile5166Val). This variant is present in population databases (rs111033419, gnomAD 0.009%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 26969326, 27460420, 32531858). ClinVar contains an entry for this variant (Variation ID: 48465). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt USH2A protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002504925 SCV002814815 uncertain significance Usher syndrome type 2A; Retinitis pigmentosa 39 2022-05-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000041788 SCV002599043 uncertain significance not specified 2025-05-23 criteria provided, single submitter clinical testing Variant summary: USH2A c.15496A>G (p.Ile5166Val) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be tolerated. The variant allele was found at a frequency of 3.6e-05 in 251472 control chromosomes. c.15496A>G has been observed in individuals affected with Usher Syndrome as a biallelic genotype or without reported second variant (e.g. Sloan-Heggen_2016, Bonnet_2016, Weisschuh_2020, Fakin_2021, Hufnagel_2022). These data indicate that the variant may be associated with disease. 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: 27460420, 34638692, 35266249, 26969326, 32531858). ClinVar contains an entry for this variant (Variation ID: 48465). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Myriad Genetics, Inc. RCV001276136 SCV002060157 uncertain significance Usher syndrome type 2A 2021-11-09 criteria provided, single submitter clinical testing NM_206933.2(USH2A):c.15496A>G(I5166V) is a missense variant classified as a variant of uncertain significance in the context of USH2A-related disorders. I5166V has been observed in cases with relevant disease (PMID: 27460420, 32531858, 26969326). Functional assessments of this variant are not available in the literature. I5166V has been observed in population frequency databases (gnomAD: NFE 0.01%). In summary, there is insufficient evidence to classify NM_206933.2(USH2A):c.15496A>G(I5166V) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041788 SCV000065484 uncertain significance not specified 2009-05-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV001276136 SCV001461988 uncertain significance Usher syndrome type 2A 2020-09-16 no assertion criteria provided clinical testing

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