ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1782del (p.Thr593_Tyr594insTer)

gnomAD frequency: 0.00001  dbSNP: rs780327716
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169497 SCV000220954 likely pathogenic Wilson disease 2014-12-13 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169497 SCV000916615 pathogenic Wilson disease 2018-02-12 criteria provided, single submitter clinical testing Variant summary: ATP7B c.1782delT (p.Tyr594X) 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 (eg.c.1820dupA/p.Phe608fsX2). The variant allele was found at a frequency of 8.1e-06 in 246350 control chromosomes. This frequency is not higher than expected for a pathogenic variant in ATP7B causing Wilson Disease (8.1e-06 vs 0.0054), allowing no conclusion about variant significance. The c.1782delT variant has been reported in the literature in multiple individuals affected with Wilson Disease. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV000169497 SCV001977364 pathogenic Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
Invitae RCV000169497 SCV002237301 pathogenic Wilson disease 2021-10-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189091). This variant is also known as 1785delT. This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 8533760, 19172127). This variant is present in population databases (rs780327716, ExAC 0.001%). This sequence change creates a premature translational stop signal (p.Tyr594*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883).

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