Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000082831 | SCV000114883 | uncertain significance | not provided | 2013-10-21 | criteria provided, single submitter | clinical testing | |
| Broad Center for Mendelian Genomics, |
RCV001723661 | SCV001950422 | uncertain significance | Retinitis pigmentosa | 2021-04-01 | criteria provided, single submitter | curation | The p.Ser2639Pro 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. |
| Labcorp Genetics |
RCV000082831 | SCV003522039 | pathogenic | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on USH2A protein function. ClinVar contains an entry for this variant (Variation ID: 96667). This missense change has been observed in individual(s) with USH2A-related conditions (PMID: 27460420, 33576794, 34148116). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs398124620, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2639 of the USH2A protein (p.Ser2639Pro). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230399 | SCV003928756 | likely pathogenic | Usher syndrome | 2023-04-05 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.7915T>C (p.Ser2639Pro) results in a non-conservative amino acid change located in the Fibronectin type III (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251098 control chromosomes (gnomAD). c.7915T>C has been reported in the literature as a biallelic genotype in multiple individuals affected with Usher Syndrome or Retinitis Pigmentosa (e.g. Bonnet_2016, Colombo_2021, Bahena_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance and one as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |