NM_000053.3(ATP7B):c.845delT (p.Leu282Profs) AND Wilson disease

Clinical significance:Pathogenic (Last evaluated: Sep 29, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000029384.1

Allele description [Variation Report for NM_000053.3(ATP7B):c.845delT (p.Leu282Profs)]

NM_000053.3(ATP7B):c.845delT (p.Leu282Profs)

Gene:
ATP7B:ATPase copper transporting beta [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q14.3
Genomic location:
Preferred name:
NM_000053.3(ATP7B):c.845delT (p.Leu282Profs)
HGVS:
  • NC_000013.11:g.51974375delA
  • NG_008806.1:g.42120delT
  • NM_000053.3:c.845delT
  • NM_001243182.1:c.802+43delT
  • NP_000044.2:p.Leu282Profs
  • NC_000013.10:g.52548511delA
  • p.Leu282ProfsX2
Links:
dbSNP: rs193922111
NCBI 1000 Genomes Browser:
rs193922111
Allele Frequency:
0.00001(-)
Molecular consequence:
  • NM_000053.3:c.845delT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001243182.1:c.802+43delT - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Wilson disease (WD)
Synonyms:
Wilson's disease; Hepatolenticular degeneration
Identifiers:
MedGen: C0019202; Orphanet: 905; OMIM: 277900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000052032Integrated Genetics/Laboratory Corporation of Americacriteria provided, single submitter
pathogenic
(Aug 18, 2011)
germlinecuration

PubMed (8)
[See all records that cite these PMIDs]

Citation Link,

SCV000752255Invitaecriteria provided, single submitter
Pathogenic
(Sep 29, 2017)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes14not providednot provided7not providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Haplotype and mutation analysis in Greek patients with Wilson disease.

Loudianos G, Dessì V, Lovicu M, Angius A, Kanavakis E, Tzetis M, Kattamis C, Manolaki N, Vassiliki G, Karpathios T, Cao A, Pirastu M.

Eur J Hum Genet. 1998 Sep-Oct;6(5):487-91.

PubMed [citation]
PMID:
9801873

Wilson disease in children: analysis of 57 cases.

Manolaki N, Nikolopoulou G, Daikos GL, Panagiotakaki E, Tzetis M, Roma E, Kanavakis E, Syriopoulou VP.

J Pediatr Gastroenterol Nutr. 2009 Jan;48(1):72-7. doi: 10.1097/MPG.0b013e31817d80b8.

PubMed [citation]
PMID:
19172127
See all PubMed Citations (10)

Details of each submission

From Integrated Genetics/Laboratory Corporation of America, SCV000052032.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedcuration PubMed (8)
2not provided10not providednot providedcuration PubMed (8)
3not provided2not providednot providedcuration PubMed (8)

Description

"A patient diagnosed with WD is homozygous for the variant; Both parents of the pt and a first cousin are all heterozygous for the variant; controls not tested."
"The variant was detected in 5 WD patients who are all homozygous for the variant; unknown if detected in controls."
"A patient diagnosed with WD is homozygous for the variant; unknown if detected in controls."

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided2not providednot providednot provided
2germlineyes5not providednot provided10not providednot providednot provided
3germlineyes1not providednot provided2not providednot providednot provided

From Invitae, SCV000752255.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Leu282Profs*2) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs193922111, ExAC 0.002%). This variant has been reported as homozygous or in combination with another ATP7B variant in several individuals affected with Wilson disease (PMID: 9311736, 9482578, 11243728, 11216666, 15523622, 18371106, 22308153). ClinVar contains an entry for this variant (Variation ID: 35735). Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jul 21, 2018