ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9469C>T (p.Gln3157Ter)

gnomAD frequency: 0.00001  dbSNP: rs772100045
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671836 SCV000796860 pathogenic Usher syndrome type 2A; Retinitis pigmentosa 39 2018-01-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000671836 SCV000893285 pathogenic Usher syndrome type 2A; Retinitis pigmentosa 39 2022-05-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000795361 SCV000934820 pathogenic not provided 2023-12-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln3157*) 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 (rs772100045, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with Usher syndrome or inherited retinal dystrophy (PMID: 23737954, 25356976, 26338283). ClinVar contains an entry for this variant (Variation ID: 555916). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844217 SCV002104140 pathogenic Usher syndrome 2022-02-04 criteria provided, single submitter clinical testing Variant summary: USH2A c.9469C>T (p.Gln3157X) 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 allele was found at a frequency of 1.6e-05 in 250496 control chromosomes (gnomAD). c.9469C>T has been reported in the literature in multiple compound heterozygous and homozygous individuals affected with Usher Syndrome or Retinitis Pigmentosa (example: Gao_2021, Shen_2021, Wafa_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: all four classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV003453335 SCV004182684 pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001273701 SCV004182685 pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV003453335 SCV004208211 pathogenic Retinitis pigmentosa 39 2023-11-11 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001273701 SCV005417690 pathogenic Usher syndrome type 2A criteria provided, single submitter clinical testing PM2_Supporting+PM3_Strong+PVS1
Natera, Inc. RCV001273701 SCV001457070 pathogenic Usher syndrome type 2A 2020-09-16 no assertion criteria provided clinical testing

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