ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.9570+1G>A (rs760225886)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666079 SCV000790318 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-03-13 criteria provided, single submitter clinical testing
Invitae RCV000808044 SCV000948130 pathogenic not provided 2018-10-10 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.
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 e.org). 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 (www.partners.org/personalized medicine/lmm).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.