NM_000053.4(ATP7B):c.1947-19T>A AND Wilson disease

Clinical significance:Likely pathogenic (Last evaluated: Feb 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001003497.1

Allele description [Variation Report for NM_000053.4(ATP7B):c.1947-19T>A]

NM_000053.4(ATP7B):c.1947-19T>A

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.1947-19T>A
HGVS:
  • NC_000013.11:g.51960341A>T
  • NG_008806.1:g.56154T>A
  • NM_000053.4:c.1947-19T>AMANE SELECT
  • NM_001005918.3:c.1870-2734T>A
  • NM_001243182.2:c.1614-19T>A
  • NM_001330578.2:c.1947-19T>A
  • NM_001330579.2:c.1870-1797T>A
  • NC_000013.10:g.52534477A>T
Links:
dbSNP: rs1593733949
NCBI 1000 Genomes Browser:
rs1593733949
Molecular consequence:
  • NM_000053.4:c.1947-19T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001005918.3:c.1870-2734T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001243182.2:c.1614-19T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001330578.2:c.1947-19T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001330579.2:c.1870-1797T>A - intron variant - [Sequence Ontology: SO:0001627]
Functional consequence:
Variation affecting splicing function of RNA [Variation Ontology: 0397]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001161426Institute for Genomic Medicine, Nationwide Children's Hospitalcriteria provided, single submitter
Likely pathogenic
(Feb 13, 2020)
inheritedresearch

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedyes1not providednot providednot providednot providedresearch

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Institute for Genomic Medicine, Nationwide Children's Hospital, SCV001161426.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedresearch PubMed (1)

Description

RNA-seq of proband liver tissue showed skipping of exons 6-7 associated with a homozygous intronic variant.

Description

This variant was identified by whole-genome sequencing of a consanguineous family in which two children carry a clinical diagnosis of Wilson disease. It is absent from the gnomAD database and segregates with WD in the family under the expected autosomal recessive inheritance model (both affected children are homozygous). Although located 19 bases into intron 5, the variant is predicted to disrupt an SC35 splicing enhancer motif and creates an hnRNP A1 splicing silencer motif according to Human Splicing Finder. RNA-seq of liver tissue from the proband demonstrated skipping of exons 6 and 7, disrupting key transmembrane and metal-binding domains. We interpret the variant as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 24, 2021

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