U.S. flag

An official website of the United States government

NM_000053.4(ATP7B):c.3547_3548del (p.Ala1183fs) AND Wilson disease

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Sep 3, 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:
RCV003062592.5

Allele description [Variation Report for NM_000053.4(ATP7B):c.3547_3548del (p.Ala1183fs)]

NM_000053.4(ATP7B):c.3547_3548del (p.Ala1183fs)

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.3547_3548del (p.Ala1183fs)
Other names:
p.Ala1183Tyrfs*2
HGVS:
  • NC_000013.11:g.51941089_51941090del
  • NG_008806.1:g.75405_75406del
  • NM_000053.4:c.3547_3548delMANE SELECT
  • NM_001005918.3:c.2926_2927del
  • NM_001243182.2:c.3214_3215del
  • NM_001330578.2:c.3313_3314del
  • NM_001330579.2:c.3295_3296del
  • NM_001406511.1:c.3547_3548delGC
  • NM_001406512.1:c.3547_3548delGC
  • NM_001406513.1:c.3541_3542delGC
  • NM_001406514.1:c.3514_3515delGC
  • NM_001406515.1:c.3493_3494delGC
  • NM_001406516.1:c.3493_3494delGC
  • NM_001406517.1:c.3451_3452delGC
  • NM_001406518.1:c.3451_3452delGC
  • NM_001406519.1:c.3412_3413delGC
  • NM_001406520.1:c.3403_3404delGC
  • NM_001406521.1:c.3403_3404delGC
  • NM_001406522.1:c.3403_3404delGC
  • NM_001406523.1:c.3364_3365delGC
  • NM_001406524.1:c.3370_3371delGC
  • NM_001406525.1:c.3352_3353delGC
  • NM_001406526.1:c.3547_3548delGC
  • NM_001406527.1:c.3313_3314delGC
  • NM_001406528.1:c.3313_3314delGC
  • NM_001406530.1:c.3307_3308delGC
  • NM_001406531.1:c.3295_3296delGC
  • NM_001406532.1:c.3295_3296delGC
  • NM_001406534.1:c.3259_3260delGC
  • NM_001406535.1:c.3217_3218delGC
  • NM_001406536.1:c.3217_3218delGC
  • NM_001406537.1:c.3208_3209delGC
  • NM_001406539.1:c.3118_3119delGC
  • NM_001406540.1:c.3100_3101delGC
  • NM_001406541.1:c.3061_3062delGC
  • NM_001406542.1:c.3061_3062delGC
  • NM_001406544.1:c.2965_2966delGC
  • NM_001406545.1:c.2899_2900delGC
  • NM_001406546.1:c.2866_2867delGC
  • NM_001406547.1:c.2704_2705delGC
  • NM_001406548.1:c.2257_2258delGC
  • NP_000044.2:p.Ala1183fs
  • NP_001005918.1:p.Ala976fs
  • NP_001230111.1:p.Ala1072fs
  • NP_001317507.1:p.Ala1105fs
  • NP_001317508.1:p.Ala1099fs
  • NP_001393440.1:p.Ala1183Tyrfs
  • NP_001393441.1:p.Ala1183Tyrfs
  • NP_001393442.1:p.Ala1181Tyrfs
  • NP_001393443.1:p.Ala1172Tyrfs
  • NP_001393444.1:p.Ala1165Tyrfs
  • NP_001393445.1:p.Ala1165Tyrfs
  • NP_001393446.1:p.Ala1151Tyrfs
  • NP_001393447.1:p.Ala1151Tyrfs
  • NP_001393448.1:p.Ala1138Tyrfs
  • NP_001393449.1:p.Ala1135Tyrfs
  • NP_001393450.1:p.Ala1135Tyrfs
  • NP_001393451.1:p.Ala1135Tyrfs
  • NP_001393452.1:p.Ala1122Tyrfs
  • NP_001393453.1:p.Ala1124Tyrfs
  • NP_001393454.1:p.Ala1118Tyrfs
  • NP_001393455.1:p.Ala1183Tyrfs
  • NP_001393456.1:p.Ala1105Tyrfs
  • NP_001393457.1:p.Ala1105Tyrfs
  • NP_001393459.1:p.Ala1103Tyrfs
  • NP_001393460.1:p.Ala1099Tyrfs
  • NP_001393461.1:p.Ala1099Tyrfs
  • NP_001393463.1:p.Ala1087Tyrfs
  • NP_001393464.1:p.Ala1073Tyrfs
  • NP_001393465.1:p.Ala1073Tyrfs
  • NP_001393466.1:p.Ala1070Tyrfs
  • NP_001393468.1:p.Ala1040Tyrfs
  • NP_001393469.1:p.Ala1034Tyrfs
  • NP_001393470.1:p.Ala1021Tyrfs
  • NP_001393471.1:p.Ala1021Tyrfs
  • NP_001393473.1:p.Ala989Tyrfs
  • NP_001393474.1:p.Ala967Tyrfs
  • NP_001393475.1:p.Ala956Tyrfs
  • NP_001393476.1:p.Ala902Tyrfs
  • NP_001393477.1:p.Ala753Tyrfs
  • NC_000013.10:g.52515225_52515226del
  • NC_000013.11:g.51941089_51941090delGC
Protein change:
A1072fs
Molecular consequence:
  • NM_000053.4:c.3547_3548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001005918.3:c.2926_2927del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001243182.2:c.3214_3215del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330578.2:c.3313_3314del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330579.2:c.3295_3296del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406511.1:c.3547_3548delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406512.1:c.3547_3548delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406513.1:c.3541_3542delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406514.1:c.3514_3515delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406515.1:c.3493_3494delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406516.1:c.3493_3494delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406517.1:c.3451_3452delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406518.1:c.3451_3452delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406519.1:c.3412_3413delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406520.1:c.3403_3404delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406521.1:c.3403_3404delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406522.1:c.3403_3404delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406523.1:c.3364_3365delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406524.1:c.3370_3371delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406525.1:c.3352_3353delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406526.1:c.3547_3548delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406527.1:c.3313_3314delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406528.1:c.3313_3314delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406530.1:c.3307_3308delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406531.1:c.3295_3296delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406532.1:c.3295_3296delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406534.1:c.3259_3260delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406535.1:c.3217_3218delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406536.1:c.3217_3218delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406537.1:c.3208_3209delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406539.1:c.3118_3119delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406540.1:c.3100_3101delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406541.1:c.3061_3062delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406542.1:c.3061_3062delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406544.1:c.2965_2966delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406545.1:c.2899_2900delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406546.1:c.2866_2867delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406547.1:c.2704_2705delGC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406548.1:c.2257_2258delGC - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003442153Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 3, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004847794Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(Jun 11, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442153.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Ala1183Tyrfs*2) 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 present in population databases (rs765139243, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Wilson’s disease (PMID: 23518715). ClinVar contains an entry for this variant (Variation ID: 2137513).

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

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847794.1

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

Description

The p.Ala1183TyrfsX2 variant in ATP7B has not been previously reported in individuals with Wilson disease but has been identified in 0.01% (1/8715) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1183 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Complete loss of ATP7B function is an established disease mechanism for Wilson disease. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Wilson disease. ACMG/AMP Criteria applied: PVS1, PM2.

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

Last Updated: Sep 29, 2024