ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.1954A>G (p.Ser652Gly)

gnomAD frequency: 0.00001  dbSNP: rs397518005
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041803 SCV000065499 uncertain significance not specified 2012-05-23 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ser652Gly varia nt in USH2A has not been reported in the literature nor previously identified by our laboratory. Computational analyses (biochemical amino acid properties, cons ervation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ser652Gly variant is not likely to impact the protein, primarily based upon a lack of conservation of the Ser652 amino acid position in other mammals; however, this information is n ot predictive enough to rule out pathogenicity. In summary, the clinical signifi cance of this variant cannot be determined with certainty; however, we would lea n towards a more likely benign role.
Labcorp Genetics (formerly Invitae), Labcorp RCV001307495 SCV001496911 uncertain significance not provided 2022-05-13 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 652 of the USH2A protein (p.Ser652Gly). This variant is present in population databases (rs397518005, gnomAD 0.002%). 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: 48480). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV003450829 SCV004182479 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001831702 SCV004182480 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004686574 SCV005181348 uncertain significance Inborn genetic diseases 2024-03-18 criteria provided, single submitter clinical testing The c.1954A>G (p.S652G) alteration is located in exon 11 (coding exon 10) of the USH2A gene. This alteration results from a A to G substitution at nucleotide position 1954, causing the serine (S) at amino acid position 652 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001831702 SCV002093969 uncertain significance Usher syndrome type 2A 2021-05-26 no assertion criteria provided clinical testing

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