Submissions for variant NM_206933.4(USH2A):c.8120G>A (p.Gly2707Glu)

gnomAD frequency: 0.00001  dbSNP: rs397518034

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041919	SCV000065615	uncertain significance	not specified	2010-09-02	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Gly2707Glu vari ant in USH2A has not been reported in the literature. We have identified it in o ne Hispanic patient without a variant on the second USH2A allele and who also ha d a single pathogenic GJB2 mutation. The Gly270 residue is conserved across spec ies and computational analyses (PolyPhen, SIFT, AlignGVGD) suggest that the Gly2 707Glu variant may impact the protein. However, this information is not predicti ve enough to assume pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty at this time.
Counsyl	RCV000666401	SCV000790687	uncertain significance	Usher syndrome type 2A; Retinitis pigmentosa 39	2017-04-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513606	SCV003450578	uncertain significance	not provided	2022-05-25	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2707 of the USH2A protein (p.Gly2707Glu). This variant is present in population databases (rs397518034, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 48593). 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. 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.
Genome-Nilou Lab	RCV003450897	SCV004182843	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001274237	SCV004182844	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001274237	SCV001458114	uncertain significance	Usher syndrome type 2A	2020-09-16	no assertion criteria provided	clinical testing