Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000670550 | SCV000795413 | pathogenic | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2017-11-17 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001057476 | SCV001221972 | pathogenic | not provided | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 48 of the USH2A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is present in population databases (rs751111524, gnomAD 0.004%). Disruption of this splice site has been observed in individuals with retinitis pigmentosa (PMID: 28041643, 28559085, 28981474). ClinVar contains an entry for this variant (Variation ID: 438033). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001075684 | SCV001241312 | pathogenic | Retinal dystrophy | 2019-04-03 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002231177 | SCV002512003 | pathogenic | Usher syndrome | 2022-04-27 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.9571-2A>G alters a conserved nucleotide located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' splice acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 250638 control chromosomes. c.9571-2A>G has been reported in the literature as compound heterozygous genotypes in multiple individuals affected with features of Usher Syndrome such as Inherited Retinal Disease (example, Stone_2017, Carss_2017, Comander_2017). 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. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Revvity Omics, |
RCV001057476 | SCV003814236 | likely pathogenic | not provided | 2022-09-26 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003446101 | SCV004172035 | likely pathogenic | Retinitis pigmentosa 39 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001829438 | SCV004172036 | likely pathogenic | Usher syndrome type 2A | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003446101 | SCV004208342 | pathogenic | Retinitis pigmentosa 39 | 2024-03-20 | criteria provided, single submitter | clinical testing | |
NIHR Bioresource Rare Diseases, |
RCV000505005 | SCV000598842 | likely pathogenic | Retinitis pigmentosa | 2015-01-01 | no assertion criteria provided | research | |
Natera, |
RCV001829438 | SCV002088395 | pathogenic | Usher syndrome type 2A | 2020-08-27 | no assertion criteria provided | clinical testing |