NM_024422.4(DSC2):c.846C>G (p.Tyr282Ter) AND Arrhythmogenic right ventricular cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Jul 20, 2012)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000039442.2

Allele description [Variation Report for NM_024422.4(DSC2):c.846C>G (p.Tyr282Ter)]

NM_024422.4(DSC2):c.846C>G (p.Tyr282Ter)

Gene:
DSC2:desmocollin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_024422.4(DSC2):c.846C>G (p.Tyr282Ter)
HGVS:
  • NC_000018.10:g.31086672G>C
  • NG_008208.2:g.20754C>G
  • NM_004949.4:c.846C>G
  • NM_024422.4:c.846C>G
  • NP_004940.1:p.Tyr282Ter
  • NP_077740.1:p.Tyr282Ter
  • LRG_400:g.20754C>G
  • LRG_400p1:p.Tyr282Ter
  • NC_000018.9:g.28666635G>C
  • NM_004949.3:c.846C>G
  • NM_024422.3:c.846C>G
  • c.846C>G
  • p.Tyr282X
  • p.Y282*:TAC>TAG
Protein change:
Y282*
Links:
dbSNP: 397517406
NCBI 1000 Genomes Browser:
rs397517406
Molecular consequence:
  • NM_004949.4:c.846C>G - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:
Arrhythmogenic right ventricular dysplasia
Identifiers:
MedGen: C0349788; OMIM: PS107970

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000063126Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Jul 20, 2012)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided41not providednot providednot providedclinical testing

Citations

PubMed

Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy.

Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, Basson CT, Lerman BB, Sasse-Klaassen S, Thierfelder L, MacRae CA, Gerull B.

Am J Hum Genet. 2006 Dec;79(6):1081-8.

PubMed [citation]
PMID:
17186466
PMCID:
PMC1698714

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000063126.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (2)

Description

The Tyr282X variant in DSC2 has not been reported in the literature nor previously identified in large and broad European American and African American populations by NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). This nonsense variant leads to a premature termination codon at position 282, which is predicted to lead to a truncated or absent protein. Variants resulting in loss of function of DSC2 have been reported in individuals with ARVC (http://arvcdatabase.info/). In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided4not provided1not provided

Last Updated: Dec 6, 2016