NM_000053.4(ATP7B):c.3552dup (p.Asp1185Ter) AND Wilson disease

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Dec 17, 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:: RCV000169520.9

Allele description [Variation Report for NM_000053.4(ATP7B):c.3552dup (p.Asp1185Ter)]

NM_000053.4(ATP7B):c.3552dup (p.Asp1185Ter)

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.3552dup (p.Asp1185Ter)

HGVS:

NC_000013.11:g.51941086dup
NG_008806.1:g.75410dup
NM_000053.4:c.3552dupMANE SELECT
NM_001005918.3:c.2931dup
NM_001243182.2:c.3219dup
NM_001330578.2:c.3318dup
NM_001330579.2:c.3300dup
NP_000044.2:p.Asp1185Ter
NP_001005918.1:p.Asp978Ter
NP_001230111.1:p.Asp1074Ter
NP_001317507.1:p.Asp1107Ter
NP_001317508.1:p.Asp1101Ter
NC_000013.10:g.52515222dup
NM_000053.3:c.3552dupT

Protein change:

D1074*

Links:

OMIM: 606882.0005; dbSNP: rs748924063

NCBI 1000 Genomes Browser:

rs748924063

Molecular consequence:

NM_000053.4:c.3552dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001005918.3:c.2931dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001243182.2:c.3219dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001330578.2:c.3318dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001330579.2:c.3300dup - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000024217	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 1993)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000220992	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Dec 29, 2014)	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 8298641, 23518715 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV004216456	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 17, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004845338	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 28, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 8298641, 21707886, 23518715, 25130000, 31059521, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	2	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.

Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, Romano DM, Parano E, Pavone L, Brzustowicz LM, et al.

Nat Genet. 1993 Dec;5(4):344-50.

PubMed [citation]

PMID:: 8298641

Potential of the international scoring system for the diagnosis of Wilson disease to differentiate Japanese patients who need anti-copper treatment.

Tatsumi Y, Shinohara T, Imoto M, Wakusawa S, Yano M, Hayashi K, Hattori A, Hayashi H, Shimizu A, Ichiki T, Nakashima S, Katano Y, Goto H.

Hepatol Res. 2011 Sep;41(9):887-96. doi: 10.1111/j.1872-034X.2011.00835.x. Epub 2011 Jun 28.

PubMed [citation]

PMID:: 21707886

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000024217.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

On 1 chromosome of an American patient with Wilson disease (WND; 277900), Tanzi et al. (1993) found insertion of an extra thymine residue after thymine 2487, resulting in a frameshift at amino acid 829. The change in the protein was in the amphiphilic helix between the phosphorylation and ATP-binding domains. The second disease allele in this patient had not been identified.

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

From Counsyl, SCV000220992.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

#	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

From Baylor Genetics, SCV004216456.2

#	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

From All of Us Research Program, National Institutes of Health, SCV004845338.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is predicted to result in loss of protein function through nonsense-mediated decay or protein truncation. Loss of function is an established mechanism of disease in Wilson disease. This variant has been reported in individuals with Wilson disease (PMID: 21707886, 25130000, 8298641). This variant is present in 1/249586 total alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). This variant was detected in one affected individual as homozygous and one as compound heterozygous (in trans) with a likely pathogenic or pathogenic variant, which is consistent with autosomal recessive inheritance (PMID: 23518715, 31059521).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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