NM_000053.4(ATP7B):c.1470C>A (p.Cys490Ter) AND Wilson disease

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 10, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000411554.3

Allele description [Variation Report for NM_000053.4(ATP7B):c.1470C>A (p.Cys490Ter)]

NM_000053.4(ATP7B):c.1470C>A (p.Cys490Ter)

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.1470C>A (p.Cys490Ter)
HGVS:
  • NC_000013.11:g.51970565G>T
  • NG_008806.1:g.45930C>A
  • NM_000053.4:c.1470C>AMANE SELECT
  • NM_001005918.3:c.1470C>A
  • NM_001243182.2:c.1137C>A
  • NM_001330578.2:c.1470C>A
  • NM_001330579.2:c.1470C>A
  • NP_000044.2:p.Cys490Ter
  • NP_001005918.1:p.Cys490Ter
  • NP_001230111.1:p.Cys379Ter
  • NP_001317507.1:p.Cys490Ter
  • NP_001317508.1:p.Cys490Ter
  • NC_000013.10:g.52544701G>T
  • NM_000053.3:c.1470C>A
Protein change:
C379*
Links:
dbSNP: rs778675259
NCBI 1000 Genomes Browser:
rs778675259
Molecular consequence:
  • NM_000053.4:c.1470C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001005918.3:c.1470C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001243182.2:c.1137C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001330578.2:c.1470C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001330579.2:c.1470C>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000485590Counsylcriteria provided, single submitter
Likely pathogenic
(Jan 14, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000918608Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Dec 10, 2018)
germlineclinical testing

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

Citation Link,

SCV001977376Nilou-Genome Labcriteria provided, single submitter
Likely pathogenic
(Aug 10, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ.

Science. 2015 Jan 9;347(6218):1254806. doi: 10.1126/science.1254806. Epub 2014 Dec 18.

PubMed [citation]
PMID:
25525159
PMCID:
PMC4362528

Six novel ATP7B mutations in Thai patients with Wilson disease.

Panichareon B, Taweechue K, Thongnoppakhun W, Aksornworanart M, Pithukpakorn M, Yenchitsomanus PT, Limwongse C, Limjindaporn T.

Eur J Med Genet. 2011 Mar-Apr;54(2):103-7. doi: 10.1016/j.ejmg.2010.10.008. Epub 2010 Oct 27.

PubMed [citation]
PMID:
21034864
See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000485590.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918608.1

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

Description

Variant summary: ATP7B c.1470C>A (p.Cys490X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. p.Gln511X, p.Ile582fsX25, p.Gln717X). The variant was absent in 246092 control chromosomes. c.1470C>A has been reported in the literature in multiple individuals affected with Wilson Disease (Tsai_1999, Cheng_2017). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

From Nilou-Genome Lab, SCV001977376.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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