VCV001878229.1 - ClinVar

NM_000053.4(ATP7B):c.436_1708-958del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000053.4(ATP7B):c.436_1708-958del

Variation ID: 1878229 Accession: VCV001878229.1

Type and length

Deletion, 8,794 bp

Location

Cytogenetic: 13q14.3 13: 51965991-51974784 (GRCh38) [ NCBI UCSC ] 13: 52540127-52548920 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 15, 2023	Jan 15, 2023	Dec 7, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000053.4:c.436_1708-958del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor splice donor
NM_001005918.3:c.436_1708-958del		splice acceptor splice donor
NM_001243182.2:c.436_1375-958del		splice acceptor splice donor
NM_001330578.2:c.436_1708-958del		splice acceptor splice donor
NM_001330579.2:c.436_1708-958del		splice acceptor splice donor
NC_000013.11:g.51965991_51974784del
NC_000013.10:g.52540127_52548920del
NG_008806.1:g.41711_50504del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ATP7B		-	-	GRCh38 GRCh37	2916	3060

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Wilson disease	Pathogenic (1)	criteria provided, single submitter	Dec 7, 2022	RCV002510282.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Dec 07, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Wilson disease Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002819305.1 First in ClinVar: Jan 15, 2023 Last updated: Jan 15, 2023	Publications: PubMed (1) PubMed: 21925265 Comment: Variant summary: The variant identified by MLPA or other technology involves the deletion of partial exon 2, and full exons 3-4 in the ATP7B gene. … (more) Variant summary: The variant identified by MLPA or other technology involves the deletion of partial exon 2, and full exons 3-4 in the ATP7B gene. A presumed nomenclature of c.436_1708-958del8794 has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a large deletion in the ATP7B gene, a known mechanism of disease. The variant was absent in 21694 control chromosomes in the gnomAD database (structural variants data set). A similar deletion (designated as c.51+384_1708-953del, HGVS c.436_1708-954del8798) has been reported in the literature in an individual affected with Wilson Disease in homozygous state (example: Incollu_2011). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. (less)

Comment:

Variant summary: The variant identified by MLPA or other technology involves the deletion of partial exon 2, and full exons 3-4 in the ATP7B gene. A presumed nomenclature of c.436_1708-958del8794 has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a large deletion in the ATP7B gene, a known mechanism of disease. The variant was absent in 21694 control chromosomes in the gnomAD database (structural variants data set). A similar deletion (designated as c.51+384_1708-953del, HGVS c.436_1708-954del8798) has been reported in the literature in an individual affected with Wilson Disease in homozygous state (example: Incollu_2011). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
DNA and RNA studies for molecular characterization of a gross deletion detected in homozygosity in the NH2-terminal region of the ATP7B gene in a Wilson disease patient.	Incollu S	Molecular and cellular probes	2011	PMID: 21925265

Text-mined citations for this variant ...

Record last updated Jan 21, 2023

ClinVar Genomic variation as it relates to human health

NM_000053.4(ATP7B):c.436_1708-958del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...