ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2009_2015del (p.Ile669_Tyr670insTer) (rs779904655)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000169214 SCV000694412 pathogenic Wilson disease 2017-02-03 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.2009_2015delATATGCT (p.Tyr670Terfs) variant results in a premature termination codon, predicted to cause a truncated or absent ATP7B 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 (e.g. c.3402delC, p.Ala1135fs). One in silico tool predicts a damaging outcome for this variant. This variant was found in 2/120512 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). The variant has been reported in affected individuals in the literature in both the homozygous and compound heterozygous state. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000169214 SCV001159414 pathogenic Wilson disease 2019-01-05 criteria provided, single submitter clinical testing The ATP7B c.2009_2015del; p.Tyr670Ter variant (rs779904655), also known as 1950-1956 deletion, has been described in individuals and families affected with Wilson disease (Bull 1993, Thomas 1995). The variant is listed in the ClinVar database (Variation ID: 188862), and is observed at a low overall frequency of 0.0024% (6/249204 alleles) in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant deletes seven nucleotides, resulting in an immediate stop codon, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. REFERENCES Bull PC et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993 Dec;5(4):327-37. Thomas GR et al. Wilsondisease in Iceland: a clinical and genetic study. Am J Hum Genet. 1995 May;56(5):1140-6.
Invitae RCV000169214 SCV001215891 pathogenic Wilson disease 2019-12-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr670*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs779904655, ExAC 0.003%). This variant has been observed to segregate with disease in families affected with Wilson disease (PMID: 7726170). This variant is also known as 2010del7 in the literature. ClinVar contains an entry for this variant (Variation ID: 188862). Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000169214 SCV000220473 pathogenic Wilson disease 2018-02-23 no assertion criteria provided clinical testing

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