ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter) (rs111033364)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 16
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824781 SCV000065401 pathogenic Usher syndrome; Rare genetic deafness 2017-10-03 criteria provided, single submitter clinical testing The p.Trp3955X variant in USH2A has been reported in many probands with Usher sy ndrome, many of whom were homozygous or compound heterozygous (van Wijk 2004, Cr emers 2007, Jacobson 2008, Dreyer 2008, Jaijo 2009, LMM data). This variant has also been identified in 0.025% (32/128914) of European chromosomes, including 1 homozygote, by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is not high enough to ru le out a pathogenic role. This nonsense variant leads to a premature termination codon at position 3955, which is predicted to lead to a truncated or absent pro tein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome. ACMG/AMP Criteria applied: PVS1, PM3_Very S trong, PP4.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000414231 SCV000344373 pathogenic not provided 2016-08-30 criteria provided, single submitter clinical testing
GeneDx RCV000414231 SCV000490872 pathogenic not provided 2018-07-24 criteria provided, single submitter clinical testing The W3955X nonsense variant in the USH2A gene has been reported previously in association with autosomal recessive Usher syndrome type 2A (van Wijk et al., 2004; Cremers et al., 2007; Le Quesne Stabej et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W3955X variant is observed in 30/126,436 (0.024%) alleles from individuals of non-Finnish European background in large population cohorts and one individual was reported to be homozygous (Lek et al., 2016). We interpret W3955X as a pathogenic variant.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414867 SCV000492761 pathogenic Hearing impairment 2014-07-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV000002451 SCV001162877 pathogenic Usher syndrome, type 2A criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000002451 SCV001194132 pathogenic Usher syndrome, type 2A 2019-12-26 criteria provided, single submitter clinical testing NM_206933.2(USH2A):c.11864G>A(W3955*) is classified as pathogenic in the context of USH2A-related disorders. Sources cited for classification include the following: PMID 27460420. Classification of NM_206933.2(USH2A):c.11864G>A(W3955*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000414231 SCV001213203 pathogenic not provided 2020-01-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp3955*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs111033364, ExAC 0.02%). This variant has been observed in several individuals with Usher syndrome (PMID: 22135276, 25575603, 29293505). ClinVar contains an entry for this variant (Variation ID: 2357). 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 RCV001074873 SCV001240477 pathogenic Retinal dystrophy 2019-08-07 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000414231 SCV001246247 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
OMIM RCV000002451 SCV000022609 pathogenic Usher syndrome, type 2A 2004-04-01 no assertion criteria provided literature only
Myriad Women's Health, Inc. RCV000002451 SCV000487751 pathogenic Usher syndrome, type 2A 2016-10-27 no assertion criteria provided clinical testing
Counsyl RCV000412373 SCV000487752 pathogenic Retinitis pigmentosa 39 2016-10-27 no assertion criteria provided clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415089 SCV000492673 pathogenic Congenital sensorineural hearing impairment 2016-02-12 no assertion criteria provided clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504922 SCV000598770 pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000504922 SCV000926715 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV001003260 SCV001161342 pathogenic Usher syndrome type 2 2019-06-23 no assertion criteria provided research

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.