ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.2809+2T>A (rs1553320397)

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
GeneDx RCV000599015 SCV000710709 likely pathogenic not provided 2018-02-16 criteria provided, single submitter clinical testing The c.2809+2T>A splice site variant in the USH2A gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant destroys the canonical splice donor site in intron 13, and is expected to cause abnormal gene splicing. This variant is not observed in large population cohorts (Lek et al., 2016). Based on currently available evidence, we consider c.2809+2T>A to be a likely pathogenic variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000605844 SCV000731690 pathogenic Rare genetic deafness 2017-06-20 criteria provided, single submitter clinical testing The c.2809+2T>A variant in USH2A has not been previously reported in individuals with hearing loss or Usher syndrome and is absent from large population databas es. This 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. Loss of function is an established disease mechanism for autosom al recessive Usher syndrome. In summary, the c.2809+2T>A variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the predicted impact to splicing.
Invitae RCV000599015 SCV001396971 likely pathogenic not provided 2019-06-08 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 13 of the USH2A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 504388). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.