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NM_000053.4(ATP7B):c.3017G>A (p.Gly1006Asp) AND Wilson disease

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Feb 27, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001882558.5

Allele description [Variation Report for NM_000053.4(ATP7B):c.3017G>A (p.Gly1006Asp)]

NM_000053.4(ATP7B):c.3017G>A (p.Gly1006Asp)

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.3017G>A (p.Gly1006Asp)
HGVS:
  • NC_000013.11:g.51946327C>T
  • NG_008806.1:g.70168G>A
  • NM_000053.4:c.3017G>AMANE SELECT
  • NM_001005918.3:c.2396G>A
  • NM_001243182.2:c.2684G>A
  • NM_001330578.2:c.2783G>A
  • NM_001330579.2:c.2765G>A
  • NP_000044.2:p.Gly1006Asp
  • NP_001005918.1:p.Gly799Asp
  • NP_001230111.1:p.Gly895Asp
  • NP_001317507.1:p.Gly928Asp
  • NP_001317508.1:p.Gly922Asp
  • NC_000013.10:g.52520463C>T
  • NM_000053.3:c.3017G>A
  • p.Gly1006Asp
Protein change:
G1006D
Links:
dbSNP: rs1184103234
NCBI 1000 Genomes Browser:
rs1184103234
Molecular consequence:
  • NM_000053.4:c.3017G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005918.3:c.2396G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243182.2:c.2684G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330578.2:c.2783G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330579.2:c.2765G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Wilson disease (WND)
Synonyms:
Wilson's disease; Hepatolenticular degeneration
Identifiers:
MONDO: MONDO:0010200; MedGen: C0019202; Orphanet: 905; OMIM: 277900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002267296Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 31, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004564352ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)		Uncertain significance
(Feb 27, 2023) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002267296.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. ClinVar contains an entry for this variant (Variation ID: 1163547). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 1006 of the ATP7B protein (p.Gly1006Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004564352.1

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

Description

The ATP7B c.3017G>A; p.Gly1006Asp variant (rs1184103234), to our knowledge, is not reported in the medical literature in individuals with Wilson disease but is reported in ClinVar (Variation ID: 1163547). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.921). Due to limited information, the clinical significance of this variant is uncertain at this time.

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

Last Updated: Sep 29, 2024