ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.5858C>G (p.Ala1953Gly) (rs41302239)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041872 SCV000065568 likely benign not specified 2019-06-28 criteria provided, single submitter clinical testing The p.Ala1953Gly variant in USH2A has been identified in several individuals with hearing loss, retinitis pigmentosa, and Usher syndrome but has been identified in 0.1% (144/128948) of European chromosomes (http://gnomad.broadinstitute.org). This frequency suggests that the variant may not be pathogenic. Consistent with this, three individuals tested by our laboratory had alternate genetic explanations of their disease, including one individual who was homozygous for the p. Ala1953Gly variant but harbored another homozygous pathogenic USH2A variant. ACMG/AMP criteria applied: BS1_Supporting, BP2, BP5.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726918 SCV000704147 uncertain significance not provided 2017-01-03 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765069 SCV000896269 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000726918 SCV000970669 likely benign not provided 2018-04-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics Inc RCV000726918 SCV001146614 uncertain significance not provided 2019-07-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000726918 SCV001147674 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing
Invitae RCV000726918 SCV001216189 uncertain significance not provided 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 1953 of the USH2A protein (p.Ala1953Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs41302239, ExAC 0.1%). This variant has been observed in individuals affected with retinitis pigmentosa, retinal dystrophy, and Usher syndrome (PMID: 28981474, 28041643, 29142287). However, in each of these individuals, three or more variants were observed in the USH2A gene, making the contribution of the p.Ala1953Gly variant unclear. ClinVar contains an entry for this variant (Variation ID: 48546). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196428 SCV001367036 uncertain significance Usher syndrome, type 2A 2019-11-28 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM1,PP3.
Nilou-Genome Lab RCV001196428 SCV001737353 uncertain significance Usher syndrome, type 2A 2021-06-10 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001579152 SCV001806576 uncertain significance Retinitis pigmentosa 39 2021-07-22 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504937 SCV000598816 uncertain significance Retinal dystrophy 2015-01-01 no assertion criteria provided research
Natera, Inc. RCV001196428 SCV001455629 uncertain significance Usher syndrome, type 2A 2019-12-31 no assertion criteria provided clinical testing

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