ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.8254G>A (p.Gly2752Arg)

gnomAD frequency: 0.00002  dbSNP: rs201863550
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004145 SCV001162879 pathogenic Usher syndrome type 2A criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073611 SCV001239162 pathogenic Retinal dystrophy 2019-07-12 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001091130 SCV001246996 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001091130 SCV001590416 pathogenic not provided 2024-05-23 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2752 of the USH2A protein (p.Gly2752Arg). This variant is present in population databases (rs201863550, gnomAD 0.02%). This missense change has been observed in individual(s) with retinitis pigmentosa and Usher syndrome (PMID: 21569298, 26806561, 27596865, 28678594, 29625443, 30459346). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 636127). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001091130 SCV002021607 likely pathogenic not provided 2021-06-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226391 SCV003922471 pathogenic Usher syndrome 2023-03-06 criteria provided, single submitter clinical testing Variant summary: USH2A c.8254G>A (p.Gly2752Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 247260 control chromosomes. c.8254G>A has been reported in the literature in multiple individuals affected with Usher Syndrome or retinitis pigmentosa. These data indicate that the variant is very likely to be associated with disease. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV003453626 SCV004182825 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001004145 SCV004182826 likely pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV003453626 SCV004208165 pathogenic Retinitis pigmentosa 39 2024-03-16 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV001073611 SCV004707928 pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Fulgent Genetics, Fulgent Genetics RCV005012311 SCV005639061 likely pathogenic Usher syndrome type 2A; Retinitis pigmentosa 39 2024-02-07 criteria provided, single submitter clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787741 SCV000926745 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research

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