NM_000053.4(ATP7B):c.3061-2A>G AND Wilson disease

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 4, 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:: RCV001046279.7

Allele description [Variation Report for NM_000053.4(ATP7B):c.3061-2A>G]

NM_000053.4(ATP7B):c.3061-2A>G

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.3061-2A>G

HGVS:

NC_000013.11:g.51944293T>C
NG_008806.1:g.72202A>G
NM_000053.4:c.3061-2A>GMANE SELECT
NM_001005918.3:c.2440-2A>G
NM_001243182.2:c.2728-2A>G
NM_001330578.2:c.2827-2A>G
NM_001330579.2:c.2809-2A>G
NM_001406511.1:c.3061-2A>G
NM_001406512.1:c.3061-2A>G
NM_001406513.1:c.3061-8A>G
NM_001406514.1:c.3028-2A>G
NM_001406515.1:c.3007-2A>G
NM_001406516.1:c.3007-2A>G
NM_001406517.1:c.2965-2A>G
NM_001406518.1:c.2965-2A>G
NM_001406519.1:c.2926-2A>G
NM_001406520.1:c.2917-2A>G
NM_001406521.1:c.2917-2A>G
NM_001406522.1:c.2917-2A>G
NM_001406523.1:c.3061-1739A>G
NM_001406524.1:c.2884-2A>G
NM_001406525.1:c.2866-2A>G
NM_001406526.1:c.3061-2A>G
NM_001406527.1:c.2827-2A>G
NM_001406528.1:c.2827-2A>G
NM_001406530.1:c.2821-2A>G
NM_001406531.1:c.2809-2A>G
NM_001406532.1:c.2809-2A>G
NM_001406534.1:c.2773-2A>G
NM_001406535.1:c.2731-2A>G
NM_001406536.1:c.2731-2A>G
NM_001406537.1:c.2722-2A>G
NM_001406538.1:c.2827-2A>G
NM_001406539.1:c.2632-2A>G
NM_001406540.1:c.2614-2A>G
NM_001406541.1:c.2575-2A>G
NM_001406542.1:c.2575-2A>G
NM_001406543.1:c.2713-2A>G
NM_001406544.1:c.2479-2A>G
NM_001406545.1:c.2413-2A>G
NM_001406546.1:c.2380-2A>G
NM_001406547.1:c.2218-2A>G
NM_001406548.1:c.1771-2A>G
NC_000013.10:g.52518429T>C
NM_000053.3:c.3061-2A>G

Links:

dbSNP: rs1957520924

NCBI 1000 Genomes Browser:

rs1957520924

Molecular consequence:

NM_001406513.1:c.3061-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406523.1:c.3061-1739A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000053.4:c.3061-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001005918.3:c.2440-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001243182.2:c.2728-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001330578.2:c.2827-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001330579.2:c.2809-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406511.1:c.3061-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406512.1:c.3061-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406514.1:c.3028-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406515.1:c.3007-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406516.1:c.3007-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406517.1:c.2965-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406518.1:c.2965-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406519.1:c.2926-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406520.1:c.2917-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406521.1:c.2917-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406522.1:c.2917-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406524.1:c.2884-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406525.1:c.2866-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406526.1:c.3061-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406527.1:c.2827-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406528.1:c.2827-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406530.1:c.2821-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406531.1:c.2809-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406532.1:c.2809-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406534.1:c.2773-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406535.1:c.2731-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406536.1:c.2731-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406537.1:c.2722-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406538.1:c.2827-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406539.1:c.2632-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406540.1:c.2614-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406541.1:c.2575-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406542.1:c.2575-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406543.1:c.2713-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406544.1:c.2479-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406545.1:c.2413-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406546.1:c.2380-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406547.1:c.2218-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406548.1:c.1771-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Homo sapiens SCAF_1103279188127 genomic scaffold, whole genome shotgun sequence
Homo sapiens SCAF_1103279188127 genomic scaffold, whole genome shotgun sequence
gi|157399278|gb|DS486036.1||gnl|WGS |SCAF_1103279188127

Nucleotide
Homo sapiens chromosome 18 genomic contig, GRCh38 reference primary assembly
Homo sapiens chromosome 18 genomic contig, GRCh38 reference primary assembly
gi|568335608|gnl|ASM:GCA_000001305. HR18_CTG1_1|gb|GL000135.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001210175	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23159873, 16199547, 10441329, 16283883, 28492532
SCV004216367	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 4, 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

SCV001210175

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 2022)

germline

clinical testing

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

SCV004216367

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 4, 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

A new ATP7B gene mutation with severe condition in two unrelated Iranian families with Wilson disease.

Dastsooz H, Dehghani SM, Imanieh MH, Haghighat M, Moini M, Fardaei M.

Gene. 2013 Feb 1;514(1):48-53. doi: 10.1016/j.gene.2012.10.085. Epub 2012 Nov 13.

PubMed [citation]

PMID:: 23159873

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001210175.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 843610). Disruption of this splice site has been observed in individuals with Wilson disease (PMID: 23159873). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 13 of the ATP7B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883).

#	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, SCV004216367.1

#	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: Oct 20, 2024

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