ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.12275G>A (p.Arg4092Lys)

gnomAD frequency: 0.00004  dbSNP: rs727505170
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Total submissions: 5
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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 RCV000156650 SCV000206371 likely benign not specified 2014-07-08 criteria provided, single submitter clinical testing p.Arg4092Lys in exon 62 of USH2A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, mouse, cat, Tasmanian devil, platypus, and several reptiles have a lysine (Lys) at this position despite high nearby amino acid conservation. In addition , computational prediction tools do not suggest a high likelihood of impact to t he protein.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000156650 SCV000221363 likely benign not specified 2016-09-28 criteria provided, single submitter research
Counsyl RCV000666738 SCV000791088 uncertain significance Usher syndrome type 2A; Retinitis pigmentosa 39 2017-04-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001238988 SCV001411831 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 4092 of the USH2A protein (p.Arg4092Lys). This variant is present in population databases (rs727505170, gnomAD 0.004%). 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: 179851). 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 lysine 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.
GeneDx RCV001238988 SCV002074032 uncertain significance not provided 2024-02-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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