NM_000053.4(ATP7B):c.2871del (p.Asn958fs) AND Wilson disease

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 16, 2024
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:: RCV002037931.7

Allele description [Variation Report for NM_000053.4(ATP7B):c.2871del (p.Asn958fs)]

NM_000053.4(ATP7B):c.2871del (p.Asn958fs)

Gene:

ATP7B:ATPase copper transporting beta [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.2871del (p.Asn958fs)

HGVS:

NC_000013.11:g.51946476del
NG_008806.1:g.70022del
NM_000053.4:c.2871delMANE SELECT
NM_001005918.3:c.2250del
NM_001243182.2:c.2538del
NM_001330578.2:c.2637del
NM_001330579.2:c.2619del
NP_000044.2:p.Asn958fs
NP_001005918.1:p.Asn751fs
NP_001230111.1:p.Asn847fs
NP_001317507.1:p.Asn880fs
NP_001317508.1:p.Asn874fs
NC_000013.10:g.52520609del
NC_000013.10:g.52520612del

Protein change:

N751fs

Links:

dbSNP: rs1957668488

NCBI 1000 Genomes Browser:

rs1957668488

Molecular consequence:

NM_000053.4:c.2871del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001005918.3:c.2250del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243182.2:c.2538del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330578.2:c.2637del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330579.2:c.2619del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002233905	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10441329, 16283883, 9199563, 10721669, 28492532
SCV004216265	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 27, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002233905

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004216265

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 27, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.

Buiakova OI, Xu J, Lutsenko S, Zeitlin S, Das K, Das S, Ross BM, Mekios C, Scheinberg IH, Gilliam TC.

Hum Mol Genet. 1999 Sep;8(9):1665-71.

PubMed [citation]

PMID:: 10441329

Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.

Gromadzka G, Schmidt HH, Genschel J, Bochow B, Rodo M, Tarnacka B, Litwin T, Chabik G, Członkowska A.

Clin Genet. 2005 Dec;68(6):524-32.

PubMed [citation]

PMID:: 16283883

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002233905.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Asn958Thrfs*9) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 9199563, 10721669). ClinVar contains an entry for this variant (Variation ID: 1453526). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004216265.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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