Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000787994 | SCV000927022 | benign | Usher syndrome | 2019-03-13 | reviewed by expert panel | curation | The filtering allele frequency of the p.Gly1301Val variant in the USH2A gene is 0.52% for South Asian chromosomes by gnomAD (183/30608 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive Usher syndrome variants (BA1). |
Laboratory for Molecular Medicine, |
RCV000041835 | SCV000065531 | likely benign | not specified | 2010-04-22 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000488230 | SCV000574821 | likely benign | not provided | 2023-07-01 | criteria provided, single submitter | clinical testing | USH2A: BP4 |
ARUP Laboratories, |
RCV000488230 | SCV000884865 | uncertain significance | not provided | 2018-06-22 | criteria provided, single submitter | clinical testing | The USH2A c.3902G>T; p.Gly1301Val variant (rs111033524) is reported in the medical literature in individuals with Usher syndrome and retinitis pigmentosa, however, one of these individuals also carried an alternate molecular explanation for disease (Bonnet 2011, Pierrache 2016). The variant is reported with discrepant classifications in the ClinVar database (Variation ID: 48509) and in the Genome Aggregation Database in 0.6% (184/30778 alleles) of the South Asian population. The glycine at this codon is moderately conserved but computational analyses (SIFT:Tolerated, PolyPhen-2: Probably Damaging) predict conflicting effects of this variant on protein structure/function. Although there is information indicating this variant may not be pathogenic, there is insufficient evidence to classify the variant with certainty. Pathogenic USH2A variants are causative for autosomal recessive Usher syndrome (MIM: 276901) and retintitis pigmentosa (MIM: 613809). References: Bonnet C et al. Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. Orphanet J Rare Dis. 2011 May 11;6:21. Pierrache LH et al. Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa. Ophthalmology. 2016 May;123(5):1151-60. |
Invitae | RCV000488230 | SCV001039111 | benign | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000986538 | SCV001135556 | benign | Usher syndrome type 2A | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000505069 | SCV001259149 | uncertain significance | Retinitis pigmentosa | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV000986538 | SCV001259150 | uncertain significance | Usher syndrome type 2A | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Ocular Genomics Institute, |
RCV001376513 | SCV001573690 | benign | Retinitis pigmentosa 39 | 2021-04-08 | criteria provided, single submitter | research | The USH2A c.3902G>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: BP5, BA1, PP3. Based on this evidence we have classified this variant as Benign. |
Genome- |
RCV000986538 | SCV001737304 | benign | Usher syndrome type 2A | 2021-06-10 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001376513 | SCV001806339 | benign | Retinitis pigmentosa 39 | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000488230 | SCV002504115 | likely benign | not provided | 2019-01-17 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Fulgent Genetics, |
RCV002496665 | SCV002809626 | likely benign | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2022-04-20 | criteria provided, single submitter | clinical testing | |
SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation | RCV000787994 | SCV003927074 | likely pathogenic | Usher syndrome | 2022-12-31 | criteria provided, single submitter | research | |
Prevention |
RCV003924993 | SCV004754830 | likely benign | USH2A-related condition | 2022-09-23 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Gene |
RCV000219904 | SCV000268767 | likely pathogenic | Usher syndrome type 1 | 2016-05-19 | no assertion criteria provided | literature only | |
NIHR Bioresource Rare Diseases, |
RCV000505069 | SCV000598808 | likely pathogenic | Retinitis pigmentosa | 2015-01-01 | no assertion criteria provided | research |