ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9459C>A (p.Cys3153Ter)

dbSNP: rs73090721
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041954 SCV000065650 pathogenic Rare genetic deafness 2012-03-12 criteria provided, single submitter clinical testing The Cys3153X variant in USH2A has been reported in one individual with Usher syn drome who was compound heterozygous with a second pathogenic USH2A variant (Le Q uesne Stabej 2012). This nonsense variant leads to a premature termination codon at position 3153, which is predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic (http ://pcpgm.partners.org/LMM).
Counsyl RCV000674717 SCV000800106 pathogenic Usher syndrome type 2A; Retinitis pigmentosa 39 2018-05-22 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075710 SCV001241338 pathogenic Retinal dystrophy 2019-04-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001388971 SCV001590165 pathogenic not provided 2023-09-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys3153*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is present in population databases (rs73090721, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of Usher syndrome and/or retinitis pigmentosa (PMID: 22135276, 28559085, 31370859). ClinVar contains an entry for this variant (Variation ID: 48628). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001388971 SCV001778423 pathogenic not provided 2021-08-01 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22135276, 28894305, 31266775, 28559085, 26164827, 31370859)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001778686 SCV002015092 pathogenic Usher syndrome 2021-10-27 criteria provided, single submitter clinical testing Variant summary: USH2A c.9459C>A (p.Cys3153X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250418 control chromosomes (gnomAD). c.9459C>A has been reported in the literature in individuals affected with Usher Syndrome and autosomal recessive Retinitis Pigmentosa (e.g. Le Quesne Stabej_2012, Sujirakul_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation RCV001778686 SCV003927108 pathogenic Usher syndrome 2022-12-31 criteria provided, single submitter research
Genome-Nilou Lab RCV003450911 SCV004182689 pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001273702 SCV004182690 pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV003450911 SCV005055767 pathogenic Retinitis pigmentosa 39 2023-12-09 criteria provided, single submitter clinical testing
Natera, Inc. RCV001273702 SCV001457071 pathogenic Usher syndrome type 2A 2020-09-16 no assertion criteria provided clinical testing

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