ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.6159del (p.Glu2054fs) (rs769838859)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000596278 SCV000702407 pathogenic not provided 2016-10-26 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001074344 SCV001239919 likely pathogenic Retinal dystrophy 2019-07-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001269147 SCV001448411 likely pathogenic Usher syndrome 2020-11-02 criteria provided, single submitter clinical testing Variant summary: USH2A c.6159delA (p.Glu2054LysfsX10) 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 allele was found at a frequency of 3.2e-05 in 251396 control chromosomes (gnomAD). c.6159delA has been reported in the literature in individuals with Retinitis Pigmentosa phenotype (e.g. Wang_2014, Sharon_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000596278 SCV001590591 pathogenic not provided 2020-07-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2054Lysfs*10) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs769838859, ExAC 0.004%). This variant has been observed in an individual affected with a USH2A-related condition (PMID: 25097241). ClinVar contains an entry for this variant (Variation ID: 497726). 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.
Counsyl RCV000667726 SCV000792222 likely pathogenic Retinitis pigmentosa 39 2017-06-12 no assertion criteria provided clinical testing
Sharon lab,Hadassah-Hebrew University Medical Center RCV001003270 SCV001161353 pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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