ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2293G>A (p.Asp765Asn)

gnomAD frequency: 0.00001  dbSNP: rs28942075
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000004059 SCV000192324 pathogenic Wilson disease 2018-03-15 criteria provided, single submitter clinical testing
Counsyl RCV000004059 SCV000486748 pathogenic Wilson disease 2016-08-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000004059 SCV001977336 pathogenic Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
Invitae RCV000004059 SCV002247011 pathogenic Wilson disease 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 765 of the ATP7B protein (p.Asp765Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Wilson disease (PMID: 15024742, 20517649). This variant is also known as Asp766Asn. ClinVar contains an entry for this variant (Variation ID: 3855). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ATP7B function (PMID: 9837819, 10942420). This variant disrupts the p.Asp765 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23843956, 30384382). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000004059 SCV002511694 pathogenic Wilson disease 2022-04-01 criteria provided, single submitter clinical testing Variant summary: ATP7B c.2293G>A (p.Asp765Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249564 control chromosomes. c.2293G>A 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. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000004059 SCV004216340 pathogenic Wilson disease 2023-09-08 criteria provided, single submitter clinical testing
OMIM RCV000004059 SCV000024225 pathogenic Wilson disease 1995-12-01 no assertion criteria provided literature only

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