ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.11954G>A (p.Trp3985Ter)

gnomAD frequency: 0.00001  dbSNP: rs397517976
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Total submissions: 9
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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 RCV000041710 SCV000065406 pathogenic Rare genetic deafness 2011-06-21 criteria provided, single submitter clinical testing The Trp3985X variant in USH2A has not been reported in the literature nor previo usly identified by our laboratory. The Trp3985X variant leads to a premature sto p codon at position 3985, which is predicted to lead to a truncated or absent pr otein. In summary, this variant meets our criteria to be classified as pathogeni c.
Counsyl RCV000669396 SCV000794144 likely pathogenic Usher syndrome type 2A; Retinitis pigmentosa 39 2017-09-15 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075329 SCV001240947 likely pathogenic Retinal dystrophy 2018-02-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852856 SCV002237021 pathogenic not provided 2023-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp3985*) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 48388). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226175 SCV003922467 likely pathogenic Usher syndrome 2023-03-17 criteria provided, single submitter clinical testing Variant summary: USH2A c.11954G>A (p.Trp3985X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251330 control chromosomes (gnomAD). To our knowledge, no occurrence of c.11954G>A in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Genome-Nilou Lab RCV003450757 SCV004182054 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003450756 SCV004182055 likely pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV003450757 SCV005055771 pathogenic Retinitis pigmentosa 39 2023-12-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV001075329 SCV005072526 pathogenic Retinal dystrophy 2020-01-01 no assertion criteria provided clinical testing

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