Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001208722 | SCV001380127 | uncertain significance | not provided | 2022-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2055 of the USH2A protein (p.Ala2055Thr). This variant also falls at the last nucleotide of exon 31, which is part of the consensus splice site for this exon. This variant is present in population databases (rs768233523, 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: 939338). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Broad Center for Mendelian Genomics, |
RCV001724266 | SCV001950429 | uncertain significance | Retinitis pigmentosa | 2021-04-01 | criteria provided, single submitter | curation | The p.Ala2055Thr variant in USH2A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM3-P. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab. |
Institute for Clinical Genetics, |
RCV001208722 | SCV004025976 | uncertain significance | not provided | 2022-02-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449654 | SCV004181699 | uncertain significance | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001828672 | SCV004181700 | uncertain significance | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001828672 | SCV002090897 | uncertain significance | Usher syndrome type 2A | 2020-07-28 | no assertion criteria provided | clinical testing |