ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2128G>A (p.Gly710Ser) (rs137853285)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000144365 SCV000192320 pathogenic Wilson disease 2013-12-20 criteria provided, single submitter clinical testing
GeneDx RCV000497757 SCV000589555 pathogenic not provided 2018-05-21 criteria provided, single submitter clinical testing The G710S variant in the ATP7B gene has been reported previously in the homozygous and compound heterozygous states in patients with Wilson disease (Waldenstrom et al., 1996; Battisti et al., 1999; Hua et al., 2016). The G710S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G710S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Functional studies of the G710S variant indicate that this variant leads to significantly decreased copper intake (Huster et al., 2012). Missense variants at the same residue (G710A, G710V) have been reported in individuals with Wilson disease (Ha-Hao et al., 1998; Cox et al., 2005) We interpret G710S as a pathogenic variant.
Invitae RCV000144365 SCV000626836 pathogenic Wilson disease 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 710 of the ATP7B protein (p.Gly710Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in multiple individuals affected with Wilson disease in the homozygous and in the compound heterozygous state (PMID: 27398169, 8938442, 16233999, 16133174, 10544227, 17433323, 15967699). ClinVar contains an entry for this variant (Variation ID: 156281). Experimental studies have shown that this missense change causes a copper transport deficiency (PMID: 22240481). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000144365 SCV000694414 pathogenic Wilson disease 2016-06-23 criteria provided, single submitter clinical testing Variant summary: The c.2128G>A (p.Gly710Ser) in ATP7B gene is a missense change that is located in a loop 2-3 of the A-domain; it involves a highly conserved nucleotide and 4/5 in silico tools predict deleterious outcome. These predictions were confirmed by results of functional studies. The variant is absent from the control population dataset of ExAC. The variant was identified in multiple affected individuals (homozygotes or compound heterozygotes) presented with a classic symptoms of a WD (lowered plasma ceruloplasmin, free serum and urinary copper concentration, and the occurrence of KayserFleischer ringscharacteristic copper deposition in the corneal periphery). The variant of interest has been reported as Pathogenic by reputable database/clinical laboratory. Taking together, the variant was classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000497757 SCV000702263 pathogenic not provided 2016-10-26 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000144365 SCV000189432 not provided Wilson disease no assertion provided not provided

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