NM_000053.4(ATP7B):c.2648_2649del (p.Val883fs) AND Wilson disease

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 7, 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:: RCV003062598.3

Allele description [Variation Report for NM_000053.4(ATP7B):c.2648_2649del (p.Val883fs)]

NM_000053.4(ATP7B):c.2648_2649del (p.Val883fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.2648_2649del (p.Val883fs)

Other names:

p.Val883Alafs*3

HGVS:

NC_000013.11:g.51950088CA[1]
NG_008806.1:g.66404TG[1]
NM_000053.4:c.2648_2649delMANE SELECT
NM_001005918.3:c.2162_2163del
NM_001243182.2:c.2315_2316del
NM_001330578.2:c.2414_2415del
NM_001330579.2:c.2396_2397del
NM_001406511.1:c.2646_2647TG[1]
NM_001406512.1:c.2646_2647TG[1]
NM_001406513.1:c.2646_2647TG[1]
NM_001406514.1:c.2613_2614TG[1]
NM_001406515.1:c.2646_2647TG[1]
NM_001406516.1:c.2646_2647TG[1]
NM_001406517.1:c.2550_2551TG[1]
NM_001406518.1:c.2550_2551TG[1]
NM_001406519.1:c.2646_2647TG[1]
NM_001406520.1:c.2502_2503TG[1]
NM_001406521.1:c.2502_2503TG[1]
NM_001406522.1:c.2502_2503TG[1]
NM_001406523.1:c.2646_2647TG[1]
NM_001406524.1:c.2469_2470TG[1]
NM_001406525.1:c.2646_2647TG[1]
NM_001406526.1:c.2646_2647TG[1]
NM_001406527.1:c.2412_2413TG[1]
NM_001406528.1:c.2412_2413TG[1]
NM_001406530.1:c.2406_2407TG[1]
NM_001406531.1:c.2394_2395TG[1]
NM_001406532.1:c.2394_2395TG[1]
NM_001406534.1:c.2412_2413TG[1]
NM_001406535.1:c.2646_2647TG[1]
NM_001406536.1:c.2316_2317TG[1]
NM_001406537.1:c.2502_2503TG[1]
NM_001406538.1:c.2412_2413TG[1]
NM_001406539.1:c.2217_2218TG[1]
NM_001406540.1:c.2394_2395TG[1]
NM_001406541.1:c.2160_2161TG[1]
NM_001406542.1:c.2160_2161TG[1]
NM_001406543.1:c.2298_2299TG[1]
NM_001406544.1:c.2064_2065TG[1]
NM_001406545.1:c.1998_1999TG[1]
NM_001406546.1:c.2160_2161TG[1]
NM_001406547.1:c.1998_1999TG[1]
NM_001406548.1:c.1356_1357TG[1]
NP_000044.2:p.Val883fs
NP_001005918.1:p.Val721fs
NP_001230111.1:p.Val772fs
NP_001317507.1:p.Val805fs
NP_001317508.1:p.Val799fs
NP_001393440.1:p.Val883Alafs
NP_001393441.1:p.Val883Alafs
NP_001393442.1:p.Val883Alafs
NP_001393443.1:p.Val872Alafs
NP_001393444.1:p.Val883Alafs
NP_001393445.1:p.Val883Alafs
NP_001393446.1:p.Val851Alafs
NP_001393447.1:p.Val851Alafs
NP_001393448.1:p.Val883Alafs
NP_001393449.1:p.Val835Alafs
NP_001393450.1:p.Val835Alafs
NP_001393451.1:p.Val835Alafs
NP_001393452.1:p.Val883Alafs
NP_001393453.1:p.Val824Alafs
NP_001393454.1:p.Val883Alafs
NP_001393455.1:p.Val883Alafs
NP_001393456.1:p.Val805Alafs
NP_001393457.1:p.Val805Alafs
NP_001393459.1:p.Val803Alafs
NP_001393460.1:p.Val799Alafs
NP_001393461.1:p.Val799Alafs
NP_001393463.1:p.Val805Alafs
NP_001393464.1:p.Val883Alafs
NP_001393465.1:p.Val773Alafs
NP_001393466.1:p.Val835Alafs
NP_001393467.1:p.Val805Alafs
NP_001393468.1:p.Val740Alafs
NP_001393469.1:p.Val799Alafs
NP_001393470.1:p.Val721Alafs
NP_001393471.1:p.Val721Alafs
NP_001393472.1:p.Val767Alafs
NP_001393473.1:p.Val689Alafs
NP_001393474.1:p.Val667Alafs
NP_001393475.1:p.Val721Alafs
NP_001393476.1:p.Val667Alafs
NP_001393477.1:p.Val453Alafs
NC_000013.10:g.52524224CA[1]
NC_000013.10:g.52524224_52524225del
NM_000053.3:c.2648_2649del

Protein change:

V721fs

Molecular consequence:

NM_000053.4:c.2648_2649del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001005918.3:c.2162_2163del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243182.2:c.2315_2316del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330578.2:c.2414_2415del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330579.2:c.2396_2397del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406511.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406512.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406513.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406514.1:c.2613_2614TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406515.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406516.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406517.1:c.2550_2551TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406518.1:c.2550_2551TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406519.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406520.1:c.2502_2503TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406521.1:c.2502_2503TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406522.1:c.2502_2503TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406523.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406524.1:c.2469_2470TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406525.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406526.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406527.1:c.2412_2413TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406528.1:c.2412_2413TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406530.1:c.2406_2407TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406531.1:c.2394_2395TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406532.1:c.2394_2395TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406534.1:c.2412_2413TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406535.1:c.2646_2647TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406536.1:c.2316_2317TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406537.1:c.2502_2503TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406538.1:c.2412_2413TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406539.1:c.2217_2218TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406540.1:c.2394_2395TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406541.1:c.2160_2161TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406542.1:c.2160_2161TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406543.1:c.2298_2299TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406544.1:c.2064_2065TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406545.1:c.1998_1999TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406546.1:c.2160_2161TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406547.1:c.1998_1999TG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406548.1:c.1356_1357TG[1] - 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
SCV003442236	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 2, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10441329, 16283883, 12885331, 26799313, 27022412, 34470610, 28492532
SCV004216303	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 7, 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

SCV003442236

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 2, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV004216303

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 7, 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 (8)

Details of each submission

From Invitae, SCV003442236.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Val883Alafs*3) 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). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 12885331, 26799313, 27022412, 34470610). This variant is not present in population databases (gnomAD no frequency).

#	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, SCV004216303.1

#	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: Feb 14, 2024

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