Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000599059 | SCV000701902 | pathogenic | not provided | 2016-10-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000599059 | SCV000709899 | pathogenic | not provided | 2021-08-30 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27535533, 33090715, 33576794, 31266775, 10729113, 25649381, 29625443, 28559085, 29588463, 15823922, 27318125, 10909849, 25525159, 26338283, 15025721, 27460420, 21686329, 15325563, 18665195) |
Laboratory for Molecular Medicine, |
RCV000592080 | SCV000710847 | pathogenic | Usher syndrome | 2019-03-19 | criteria provided, single submitter | clinical testing | The p.Arg626X variant in USH2A has been reported >15 individuals with Usher syndrome, at least 9 of whom were homozygous or compound heterozygous with a second pathogenic USH2A variant on the other allele, and segregated in the compound heterozygous state in one affected relative (Weston 2000, Ouyang 2004, Seyedahmadi 2004, Ebermann 2009, Xu 2011, Jiang 2015, Lenassi 2015, Bonnet 2016). This variant has also been identified in 0.006% (7/113672) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 626, which is predicted to lead to a truncated or absent protein. Loss of function of the USH2A gene is an established disease mechanism in autosomal recessive Usher syndrome. In summary, this variant meets criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner based on the predicted impact of the variant and multiple occurrences with pathogenic USH2A variants in individuals with Usher syndrome. ACMG/AMP Criteria applied: PM3_VeryStrong, PVS1, PM2, PP1. |
Invitae | RCV000599059 | SCV000959652 | pathogenic | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg626*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is present in population databases (rs534534437, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with USH2A-related conditions (PMID: 10729113, 15823922, 21686329, 25649381). ClinVar contains an entry for this variant (Variation ID: 497414). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001074303 | SCV001239876 | pathogenic | Retinal dystrophy | 2019-06-19 | criteria provided, single submitter | clinical testing | |
Ocular Genomics Institute, |
RCV001376324 | SCV001573431 | pathogenic | Retinitis pigmentosa 39 | 2021-04-08 | criteria provided, single submitter | research | The USH2A c.1876C>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: PVS1, PM2, PM3, PP1, PP3. Based on this evidence we have classified this variant as Pathogenic. |
Kariminejad - |
RCV001814193 | SCV001755357 | pathogenic | Ear malformation | 2021-07-10 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000599059 | SCV002020851 | pathogenic | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV001271237 | SCV002767837 | pathogenic | Usher syndrome type 2A | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Usher syndrome (MIM#276901). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (7 heterozygotes, 0 homozygotes). (SP) 0701 - Many other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in patients with Usher syndrome (MIM#276901) and Retinitis pigments (MIM#613809) (ClinVar, PMID: 27460420). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Fulgent Genetics, |
RCV002506407 | SCV002816402 | pathogenic | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2022-01-05 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001376324 | SCV004182492 | pathogenic | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001271237 | SCV004182493 | pathogenic | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001376324 | SCV004207687 | pathogenic | Retinitis pigmentosa 39 | 2023-10-31 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001271237 | SCV001452253 | pathogenic | Usher syndrome type 2A | 2020-09-16 | no assertion criteria provided | clinical testing |