Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000373313 | SCV000340407 | uncertain significance | not provided | 2016-03-16 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000670917 | SCV000795833 | uncertain significance | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2017-11-20 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000826074 | SCV000967569 | uncertain significance | not specified | 2018-10-23 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Ser2492Leu va riant in USH2A has been reported in 1 individual with retinitis pigmentosa who a lso harbored the p.Glu767fs pathogenic variant; however, the phasing of these va riants was not determined (Carss 2017). This variant has also been identified in 0.005% (1/19894) of East Asian chromosomes and 0.003% (4/128566) of European ch romosomes by gnomAD (http://gnomad.broadinstitute.org). Serine (Ser) at position 2492 is poorly conserved across species, with three mammals (rat, naked mole ra t, and Bactrian camel) carrying a leucine (Leu) at this position. In addition, c omputational prediction tools and conservation analysis suggest that this varian t may not impact the protein, though this information is not predictive enough t o rule out pathogenicity. In summary, although the clinical significance of the p.Ser2492Leu variant is uncertain, the lack of conservation suggests it is more likely to be benign. ACMG/AMP Criteria applied: PM2, PM3_Supporting, BP4_Strong. |
Blueprint Genetics | RCV001073464 | SCV001239006 | uncertain significance | Retinal dystrophy | 2019-03-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000373313 | SCV001829138 | likely pathogenic | not provided | 2022-11-21 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28041643, 34426522, 32675063, 35266249) |
Labcorp Genetics |
RCV000373313 | SCV003280880 | uncertain significance | not provided | 2022-06-10 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2492 of the USH2A protein (p.Ser2492Leu). This variant is present in population databases (rs483353056, gnomAD 0.005%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 28041643). ClinVar contains an entry for this variant (Variation ID: 286836). 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 leucine 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. |
NIHR Bioresource Rare Diseases, |
RCV000504866 | SCV000598827 | uncertain significance | Retinitis pigmentosa | 2015-01-01 | no assertion criteria provided | research | |
Natera, |
RCV001274241 | SCV001458121 | uncertain significance | Usher syndrome type 2A | 2020-09-16 | no assertion criteria provided | clinical testing |