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

gnomAD frequency: 0.00002  dbSNP: rs201863550

Total submissions: 12

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