ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.7595-3C>G (rs201657446)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000178475 SCV000230558 likely pathogenic not provided 2014-06-26 criteria provided, single submitter clinical testing
Counsyl RCV000669197 SCV000793926 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-09-12 criteria provided, single submitter clinical testing
Invitae RCV000178475 SCV001202174 pathogenic not provided 2020-10-19 criteria provided, single submitter clinical testing This sequence change falls in intron 40 of the USH2A gene. It does not directly change the encoded amino acid sequence of the USH2A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Usher syndrome type II (PMID: 17405132, 22135276, 24944099, 25097241, 26969326). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 197447). Experimental studies have shown that this variant disrupts mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20052763). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075871 SCV001241512 pathogenic Retinal dystrophy 2019-08-14 criteria provided, single submitter clinical testing
GeneDx RCV000178475 SCV001811549 pathogenic not provided 2019-08-07 criteria provided, single submitter clinical testing Published functional studies demonstrate abnormal gene splicing with the creation of a new AG motif in intron 40 predicted to cause the insertion of intronic sequences resulting in an open reading frameshift of the transcript compared with wild-type (Le Guedard-Mereuze et al., 2010); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31589614, 32581362, 32176120, 28041643, 28981474, 26969326, 17405132, 20052763, 27460420, 22135276, 25097241, 25649381, 27208204, 24944099)
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504696 SCV000598829 likely pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research
Genomics England Pilot Project,Genomics England RCV001542728 SCV001760013 pathogenic Usher syndrome, type 2A no assertion criteria provided clinical testing

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