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NM_000053.4(ATP7B):c.2906G>A (p.Arg969Gln) AND ATP7B-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 28, 2023
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003904804.2

Allele description [Variation Report for NM_000053.4(ATP7B):c.2906G>A (p.Arg969Gln)]

NM_000053.4(ATP7B):c.2906G>A (p.Arg969Gln)

Gene:
ATP7B:ATPase copper transporting beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q14.3
Genomic location:
Preferred name:
NM_000053.4(ATP7B):c.2906G>A (p.Arg969Gln)
HGVS:
  • NC_000013.11:g.51946438C>T
  • NG_008806.1:g.70057G>A
  • NM_000053.4:c.2906G>AMANE SELECT
  • NM_001005918.3:c.2285G>A
  • NM_001243182.2:c.2573G>A
  • NM_001330578.2:c.2672G>A
  • NM_001330579.2:c.2654G>A
  • NP_000044.2:p.Arg969Gln
  • NP_001005918.1:p.Arg762Gln
  • NP_001230111.1:p.Arg858Gln
  • NP_001317507.1:p.Arg891Gln
  • NP_001317508.1:p.Arg885Gln
  • NC_000013.10:g.52520574C>T
  • NM_000053.3:c.2906G>A
  • P35670:p.Arg969Gln
Protein change:
R762Q; ARG969GLN
Links:
UniProtKB: P35670#VAR_000747; OMIM: 606882.0018; dbSNP: rs121907996
NCBI 1000 Genomes Browser:
rs121907996
Molecular consequence:
  • NM_000053.4:c.2906G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005918.3:c.2285G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243182.2:c.2573G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330578.2:c.2672G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330579.2:c.2654G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
ATP7B-related disorder
Synonyms:
ATP7B-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004719647PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Nov 28, 2023) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004719647.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ATP7B c.2906G>A variant is predicted to result in the amino acid substitution p.Arg969Gln. This variant has been reported in the homozygous state and in the heterzogyous state with a second pathogenic variant in multiple individuals with Wilson disease (see for example, Figus et al. 1995. PubMed ID: 8533760; Panagiotakaki et al. 2004. PubMed ID: 15523622; Zhang et al. 2022. PubMed ID: 35220961). Although one in vitro study found the p.Arg969Gln variant had copper transport activity similar to wild type (Schushan et al. 2012. PubMed ID: 22692182), two other studies have reported moderate to complete loss of transport function (Huster et al. 2012. PubMed ID: 22240481; Das et al. 2022. PubMed ID: 35762218). Furthermore, ATP7A protein with the p.Arg969Gln variant has been shown to have reduced expression relative to wild type and improper cellular localization to the endoplasmic reticulum (Das et al. 2022. PubMed ID: 35762218). This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD. Of note, a different missense variant at the same amino acid position (p.Arg969Trp) has also been reported in an individual with Wilson disease (Lepori et al. 2007. PubMed ID: 17949296). Taken together, this variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024