ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.949C>A (p.Arg317=) (rs111033272)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824799 SCV000065652 pathogenic Rare genetic deafness 2012-11-19 criteria provided, single submitter clinical testing The p.Arg317Arg (NM_206933.2 c.949C>A) variant in USH2A has been reported in 9 i ndividuals with Usher syndrome (Pennings 2004, Seyedahmadi 2004, Cremers 2007, D reyer 2008, Vache 2010, Bonnet 2011). A second variant in USH2A was found in tr ans in at least 3 of these individuals (Pennings 2004, Vache 2010, Bonnet 2011). This variant has also been reported in ClinVar (Variation ID#2358) as pathogeni c. mRNA studies show that this variant leads to abnormal splicing and a frameshi ft (Vache 2010). This variant has been identified in (8/126206) of European chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs111033272). Although this variant has been seen in the general pop ulation, its frequency is low enough to be consistent with a recessive carrier f requency. In summary, this variant meets criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner based upon functional evide nce and its occurrence in individuals with this disease. ACMG/AMP Criteria appli ed: PVS1, PM2, PM3, PP5.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000412796 SCV000339779 pathogenic not provided 2016-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000412796 SCV000490867 pathogenic not provided 2015-05-22 criteria provided, single submitter clinical testing The R317R variant in the USH2A gene has been reported several times previously in association with Usher syndrome type 2A (Pennings et al., 2004; Seyedahmadi et al., 2004; Cremers et al., 2007; Dreyer et al., 2008; Bonnet et al., 2011). A second pathogenic variant was identified in trans in the USH2A gene, in several of these reported patients. This variant is predicted to create a cryptic donor site upstream of the natural splice donor site for exon 6. The c.949 C>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret this variant as pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000627017 SCV000747720 pathogenic Blindness; Rod-cone dystrophy; Pigmentary retinopathy; Abnormal macular morphology; Retinal pigment epithelial atrophy 2017-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763297 SCV000893962 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000412796 SCV001219336 pathogenic not provided 2019-12-16 criteria provided, single submitter clinical testing This sequence change affects codon 317 of the USH2A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the USH2A protein. This variant is present in population databases (rs111033272, ExAC 0.003%). This variant has been observed in individual(s) with Usher syndrome type IIa or nonsydromic retinitis pigmentosa (PMID: 15241801, 26927203, 21569298, 20513143). 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: 2358). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 20513143). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075725 SCV001241353 pathogenic Retinal dystrophy 2019-05-09 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000412796 SCV001248865 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
OMIM RCV000002452 SCV000022610 pathogenic Usher syndrome, type 2A 2004-04-01 no assertion criteria provided literature only
Counsyl RCV000002452 SCV001132312 likely pathogenic Usher syndrome, type 2A 2019-01-24 no assertion criteria provided clinical testing
Counsyl RCV000984234 SCV001132313 likely pathogenic Retinitis pigmentosa 39 2019-01-24 no assertion criteria provided clinical testing

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.