ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9570+1G>A (rs760225886)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000217703 SCV000271476 pathogenic Rare genetic deafness 2015-04-17 criteria provided, single submitter clinical testing The c.9570+1G>A variant in USH2A has been reported in 4 Chinese individuals: 2 w ith Usher syndrome, 1 with hearing loss, and 1 with retinitis pigmentosa, and se gregated with disease in at least 3 affected individuals from 3 families (Huang 2013, Yang 2013, Xu 2014, Qu 2014). All of these individuals were compound hete rozygous. In addition, this variant has been identified in 7/8606 of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut Although this variant has been seen in the general population, its freq uency is low enough to be consistent with a recessive carrier frequency. The c.9 570+1G>A variant occurs in the invariant region (+/- 1,2) of the splice consensu s sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. In summary, this variant meets our criteria to be classified as pathogenic for autosomal recessive Usher syndrome ( medicine/lmm).
Invitae RCV000808044 SCV000948130 pathogenic not provided 2020-10-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 48 of the USH2A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs760225886, ExAC 0.08%). This variant has been observed in individuals with USH2A-related diseases, and has been shown to segregate with Usher syndrome in a family (PMID: 23737954, 23767834, 24938718). This variant is also known as IVS48+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 228418). Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073320 SCV001238859 pathogenic Retinal dystrophy 2018-11-20 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000666079 SCV001573408 pathogenic Retinitis pigmentosa 39 2021-04-08 criteria provided, single submitter research The USH2A c.9570+1G>A 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, PP3, PP1-M. Based on this evidence we have classified this variant as Pathogenic.
GeneDx RCV000808044 SCV001821035 pathogenic not provided 2020-11-16 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30948794, 24938718, 25252889, 23737954, 23767834)
Counsyl RCV000666079 SCV000790318 pathogenic Retinitis pigmentosa 39 2017-03-13 no assertion criteria provided clinical testing

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