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NM_000053.4(ATP7B):c.4022-2A>C AND Wilson disease

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Oct 2, 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:
RCV000669218.3

Allele description [Variation Report for NM_000053.4(ATP7B):c.4022-2A>C]

NM_000053.4(ATP7B):c.4022-2A>C

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.4022-2A>C
HGVS:
  • NC_000013.11:g.51935697T>G
  • NG_008806.1:g.80798A>C
  • NM_000053.4:c.4022-2A>CMANE SELECT
  • NM_001005918.3:c.3401-2A>C
  • NM_001243182.2:c.3689-2A>C
  • NM_001330578.2:c.3788-2A>C
  • NM_001330579.2:c.3770-2A>C
  • NM_001406511.1:c.4022-2A>C
  • NM_001406512.1:c.4022-2A>C
  • NM_001406513.1:c.4016-2A>C
  • NM_001406514.1:c.3989-2A>C
  • NM_001406515.1:c.3968-2A>C
  • NM_001406516.1:c.3968-2A>C
  • NM_001406517.1:c.3926-2A>C
  • NM_001406518.1:c.3926-2A>C
  • NM_001406519.1:c.3887-2A>C
  • NM_001406520.1:c.3878-2A>C
  • NM_001406521.1:c.3878-2A>C
  • NM_001406522.1:c.3878-2A>C
  • NM_001406523.1:c.3839-2A>C
  • NM_001406524.1:c.3845-2A>C
  • NM_001406525.1:c.3827-2A>C
  • NM_001406526.1:c.3818-2A>C
  • NM_001406527.1:c.3788-2A>C
  • NM_001406528.1:c.3788-2A>C
  • NM_001406530.1:c.3782-2A>C
  • NM_001406531.1:c.3770-2A>C
  • NM_001406532.1:c.3770-2A>C
  • NM_001406534.1:c.3734-2A>C
  • NM_001406535.1:c.3692-2A>C
  • NM_001406536.1:c.3692-2A>C
  • NM_001406537.1:c.3683-2A>C
  • NM_001406538.1:c.3644-2A>C
  • NM_001406539.1:c.3593-2A>C
  • NM_001406540.1:c.3575-2A>C
  • NM_001406541.1:c.3536-2A>C
  • NM_001406542.1:c.3536-2A>C
  • NM_001406543.1:c.3530-2A>C
  • NM_001406544.1:c.3440-2A>C
  • NM_001406545.1:c.3374-2A>C
  • NM_001406546.1:c.3341-2A>C
  • NM_001406547.1:c.3179-2A>C
  • NM_001406548.1:c.2732-2A>C
  • NC_000013.10:g.52509833T>G
  • NM_000053.3:c.4022-2A>C
Links:
dbSNP: rs1555282816
NCBI 1000 Genomes Browser:
rs1555282816
Molecular consequence:
  • NM_000053.4:c.4022-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001005918.3:c.3401-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001243182.2:c.3689-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001330578.2:c.3788-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001330579.2:c.3770-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406511.1:c.4022-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406512.1:c.4022-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406513.1:c.4016-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406514.1:c.3989-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406515.1:c.3968-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406516.1:c.3968-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406517.1:c.3926-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406518.1:c.3926-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406519.1:c.3887-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406520.1:c.3878-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406521.1:c.3878-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406522.1:c.3878-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406523.1:c.3839-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406524.1:c.3845-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406525.1:c.3827-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406526.1:c.3818-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406527.1:c.3788-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406528.1:c.3788-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406530.1:c.3782-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406531.1:c.3770-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406532.1:c.3770-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406534.1:c.3734-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406535.1:c.3692-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406536.1:c.3692-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406537.1:c.3683-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406538.1:c.3644-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406539.1:c.3593-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406540.1:c.3575-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406541.1:c.3536-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406542.1:c.3536-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406543.1:c.3530-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406544.1:c.3440-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406545.1:c.3374-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406546.1:c.3341-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406547.1:c.3179-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406548.1:c.2732-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

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
SCV000793949Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))		Likely pathogenic
(Sep 5, 2017) 		unknownclinical testing

Citation Link,

SCV004836843All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(Oct 2, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Critical roles for the COOH terminus of the Cu-ATPase ATP7B in protein stability, trans-Golgi network retention, copper sensing, and retrograde trafficking.

Braiterman L, Nyasae L, Leves F, Hubbard AL.

Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G69-81. doi: 10.1152/ajpgi.00038.2011. Epub 2011 Mar 31.

PubMed [citation]
PMID:
21454443
PMCID:
PMC3129927

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Counsyl, SCV000793949.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004836843.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

This variant causes an A to C nucleotide substitution at the -2 position of intron 19 the ATP7B protein. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies in the literature, this variant is expected to result in a truncated protein product missing the functionally important C-terminal sequence of the gene (PMID: 21454443). This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATP7B function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: May 7, 2024