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NM_001943.3(DSG2):c.1880-2A>G AND Arrhythmogenic right ventricular cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Aug 5, 2009)

Review status:1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000037276.1

Allele description

NM_001943.3(DSG2):c.1880-2A>G

Gene:
DSG2:desmoglein 2 [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_001943.3(DSG2):c.1880-2A>G
HGVS:
  • NC_000018.10:g.31541191A>G
  • NG_007072.3:g.47950A>G
  • NM_001943.3:c.1880-2A>G
  • NC_000018.9:g.29121154A>G
  • c.1880-2A>G
Nucleotide change:
IVS12AS, A-G, -2
Links:
OMIM: 125671.0008; dbSNP: 397514038
NCBI 1000 Genomes Browser:
rs397514038
Molecular consequence:
  • NM_001943.3:c.1880-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Synonyms:
Cardiomyopathy; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 10; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy12; See all synonyms [MedGen]
Identifiers:
MedGen: C0349788

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000060933Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicineclassified by single submitterprobably pathogenic
(Aug 5, 2009)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy.

Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A, Frigo G, Vettori A, Valente M, Towbin J, Thiene G, Danieli GA, Rampazzo A.

Circulation. 2006 Mar 7;113(9):1171-9. Epub 2006 Feb 27.

PubMed [citation]
PMID:
16505173

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000060933.1

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

Description

The 1880-2A>G variant has been reported in two siblings with ARVC and was absent from 560 matched control chromosomes, supporting a pathogenic role. However, both siblings also carried a second, possibly disease causing variant on the other copy of the DSG2 gene (Pilichou, 2006). RNA studies demonstrated that the 1880-2A>G abolishes the splice site, leading to the use of a cryptic splice site 38 bp downstream. The aberrantly spliced mRNA was shown to lack the first 38 bp of exon 13, which is predicted to cause a frameshift starting at position 627 and premature termination 19 amino acids later, leading to a truncated or absent protein (Pilichou, 2006). In summary, the severity of the change as well as absence from controls suggest that this variant is likely pathogenic.

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

Last Updated: Dec 19, 2014