Submissions for variant NM_206933.4(USH2A):c.6050G>A (p.Gly2017Asp)

gnomAD frequency: 0.00001  dbSNP: rs397518024

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041877	SCV000065573	uncertain significance	not specified	2011-02-08	criteria provided, single submitter	clinical testing	The Gly2017Asp variant in USH2A has not been reported in the literature. This re sidue is conserved across species and computational analyses (PolyPhen2, SIFT, A lignGVGD, MAPP) suggest that the Gly2017Asp variant may impact the protein. Howe ver, this information is not predictive enough to assume pathogenicity. It shoul d be noted that this lab has only sequenced the USH2A gene in 16 Asian probands and no Asian healthy controls. In addition, healthy control information is unava ilable from either public databases or scientific literature, such that the full spectrum of benign variation has not yet been defined for this population. Futu re analysis could reveal that the Gly2017Asp variant is common in this populatio n and therefore unlikely to be pathogenic. In summary, the clinical significance of this variant cannot be determined with certainty at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852860	SCV002212104	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2017 of the USH2A protein (p.Gly2017Asp). This variant is present in population databases (rs397518024, gnomAD 0.04%). 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: 48551). 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	RCV003450864	SCV004181724	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001831705	SCV004181726	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831705	SCV002090902	uncertain significance	Usher syndrome type 2A	2019-11-11	no assertion criteria provided	clinical testing