Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000217075 | SCV000271177 | likely benign | not specified | 2015-04-21 | criteria provided, single submitter | clinical testing | p.Ser2498Arg in exon 40 of USH2A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, >35 mammalian species have an arginine (Arg) at this position despite hig h nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. It has also been identi fied in 4/66556 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). |
| Counsyl | RCV000666814 | SCV000791171 | uncertain significance | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2017-05-01 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001812236 | SCV001473242 | uncertain significance | not provided | 2019-08-26 | criteria provided, single submitter | clinical testing | The USH2A c.7494T>A; p.Ser2498Arg variant (rs760977747), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is reported in the ClinVar database (Variation ID: 228223) and is listed in the general population with an overall allele frequency of 0.003% (8/250,694 alleles) in the Genome Aggregation Database. The serine at this position is weakly conserved, with several other mammalian species with arginine at this position, and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. However, given the lack of clinical and functional data, the significance of the p.Ser2498Arg variant is uncertain at this time. |
| Invitae | RCV001812236 | SCV003456329 | uncertain significance | not provided | 2022-07-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 2498 of the USH2A protein (p.Ser2498Arg). This variant is present in population databases (rs760977747, gnomAD 0.007%). 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: 228223). 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 arginine 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. |
| Ambry Genetics | RCV002517521 | SCV003722297 | likely benign | Inborn genetic diseases | 2022-02-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Natera, |
RCV001271980 | SCV001453608 | uncertain significance | Usher syndrome type 2A | 2020-01-17 | no assertion criteria provided | clinical testing |