NM_000053.4(ATP7B):c.768_771dup (p.Thr258fs) AND Wilson disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003503894.2

Allele description [Variation Report for NM_000053.4(ATP7B):c.768_771dup (p.Thr258fs)]

NM_000053.4(ATP7B):c.768_771dup (p.Thr258fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.768_771dup (p.Thr258fs)

HGVS:

NC_000013.11:g.51974449_51974452dup
NG_008806.1:g.42043_42046dup
NM_000053.4:c.768_771dupMANE SELECT
NM_001005918.3:c.768_771dup
NM_001243182.2:c.768_771dup
NM_001330578.2:c.768_771dup
NM_001330579.2:c.768_771dup
NM_001406511.1:c.768_771dup
NM_001406512.1:c.768_771dup
NM_001406513.1:c.768_771dup
NM_001406514.1:c.768_771dup
NM_001406515.1:c.768_771dup
NM_001406516.1:c.768_771dup
NM_001406517.1:c.672_675dup
NM_001406518.1:c.672_675dup
NM_001406519.1:c.768_771dup
NM_001406520.1:c.768_771dup
NM_001406521.1:c.768_771dup
NM_001406522.1:c.768_771dup
NM_001406523.1:c.768_771dup
NM_001406524.1:c.768_771dup
NM_001406525.1:c.768_771dup
NM_001406526.1:c.768_771dup
NM_001406527.1:c.768_771dup
NM_001406528.1:c.768_771dup
NM_001406530.1:c.672_675dup
NM_001406531.1:c.768_771dup
NM_001406532.1:c.768_771dup
NM_001406534.1:c.768_771dup
NM_001406535.1:c.768_771dup
NM_001406536.1:c.672_675dup
NM_001406537.1:c.768_771dup
NM_001406538.1:c.768_771dup
NM_001406539.1:c.672_675dup
NM_001406540.1:c.768_771dup
NM_001406541.1:c.768_771dup
NM_001406542.1:c.768_771dup
NM_001406543.1:c.672_675dup
NM_001406544.1:c.672_675dup
NM_001406545.1:c.768_771dup
NM_001406546.1:c.768_771dup
NM_001406547.1:c.768_771dup
NM_001406548.1:c.768_771dup
NP_000044.2:p.Thr258fs
NP_001005918.1:p.Thr258fs
NP_001230111.1:p.Thr258fs
NP_001317507.1:p.Thr258fs
NP_001317508.1:p.Thr258fs
NP_001393440.1:p.Thr258fs
NP_001393441.1:p.Thr258fs
NP_001393442.1:p.Thr258fs
NP_001393443.1:p.Thr258fs
NP_001393444.1:p.Thr258fs
NP_001393445.1:p.Thr258fs
NP_001393446.1:p.Thr226fs
NP_001393447.1:p.Thr226fs
NP_001393448.1:p.Thr258fs
NP_001393449.1:p.Thr258fs
NP_001393450.1:p.Thr258fs
NP_001393451.1:p.Thr258fs
NP_001393452.1:p.Thr258fs
NP_001393453.1:p.Thr258fs
NP_001393454.1:p.Thr258fs
NP_001393455.1:p.Thr258fs
NP_001393456.1:p.Thr258fs
NP_001393457.1:p.Thr258fs
NP_001393459.1:p.Thr226fs
NP_001393460.1:p.Thr258fs
NP_001393461.1:p.Thr258fs
NP_001393463.1:p.Thr258fs
NP_001393464.1:p.Thr258fs
NP_001393465.1:p.Thr226fs
NP_001393466.1:p.Thr258fs
NP_001393467.1:p.Thr258fs
NP_001393468.1:p.Thr226fs
NP_001393469.1:p.Thr258fs
NP_001393470.1:p.Thr258fs
NP_001393471.1:p.Thr258fs
NP_001393472.1:p.Thr226fs
NP_001393473.1:p.Thr226fs
NP_001393474.1:p.Thr258fs
NP_001393475.1:p.Thr258fs
NP_001393476.1:p.Thr258fs
NP_001393477.1:p.Thr258fs
NC_000013.10:g.52548584_52548585insGACC
NC_000013.10:g.52548585_52548588dup

Protein change:

T226fs

Molecular consequence:

NM_000053.4:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001005918.3:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243182.2:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330578.2:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330579.2:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406511.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406512.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406513.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406514.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406515.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406516.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406517.1:c.672_675dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406518.1:c.672_675dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406519.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406520.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406521.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406522.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406523.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406524.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406525.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406526.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406527.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406528.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406530.1:c.672_675dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406531.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406532.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406534.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406535.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406536.1:c.672_675dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406537.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406538.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406539.1:c.672_675dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406540.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406541.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406542.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406543.1:c.672_675dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406544.1:c.672_675dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406545.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406546.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406547.1:c.768_771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406548.1:c.768_771dup - 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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Mus musculus serine (or cysteine) peptidase inhibitor, clade A, member 6 (Serpin...
Mus musculus serine (or cysteine) peptidase inhibitor, clade A, member 6 (Serpina6), mRNA
gi|927442693|ref|NM_007618.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004270782	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10441329, 16283883, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004270782

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004270782.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Thr258Glyfs*13) 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 variant has not been reported in the literature in individuals affected with ATP7B-related conditions. 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

Last Updated: Sep 29, 2024

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