NM_001943.5(DSG2):c.523+2T>C AND Arrhythmogenic right ventricular cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Feb 21, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000037309.4

Allele description [Variation Report for NM_001943.5(DSG2):c.523+2T>C]

NM_001943.5(DSG2):c.523+2T>C

Gene:
DSG2:desmoglein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_001943.5(DSG2):c.523+2T>C
HGVS:
  • NC_000018.10:g.31521245T>C
  • NG_007072.3:g.28004T>C
  • NM_001943.5:c.523+2T>CMANE SELECT
  • LRG_397t1:c.523+2T>C
  • LRG_397:g.28004T>C
  • NC_000018.9:g.29101208T>C
  • NM_001943.3:c.523+2T>C
  • c.523+2T>C
Links:
dbSNP: rs397516709
NCBI 1000 Genomes Browser:
rs397516709
Molecular consequence:
  • NM_001943.5:c.523+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
4

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:
Cardiomyopathy, ARVC; Arrhythmogenic right ventricular dysplasia
Identifiers:
MONDO: MONDO:0016587; MedGen: C0349788; OMIM: PS107970

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000060966Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Feb 21, 2018)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided54not 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

Incremental value of cardiac magnetic resonance imaging in arrhythmic risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers.

te Riele AS, Bhonsale A, James CA, Rastegar N, Murray B, Burt JR, Tichnell C, Madhavan S, Judge DP, Bluemke DA, Zimmerman SL, Kamel IR, Calkins H, Tandri H.

J Am Coll Cardiol. 2013 Nov 5;62(19):1761-9. doi: 10.1016/j.jacc.2012.11.087. Epub 2013 Jun 27.

PubMed [citation]
PMID:
23810894
PMCID:
PMC3971056
See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000060966.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (6)

Description

The c.523+2T>C variant in DSG2 has been reported in 6 individuals with clinical features of arrhythmogenic right ventricular cardiomyopathy (ARVC; Fressart 2010 , Tan 2010, LMM unpublished data). This variant has been identified in 2/105830 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.b roadinstitute.org; dbSNP rs397516709) and reported in ClinVar (Variation ID 4432 1). c.523+2T>C variant occurs in the invariant region (+/- 1,2) of the splice co nsensus sequence and is predicted to cause altered splicing leading to an abnorm al or absent protein. Heterozygous loss of function of the DSG2 gene has been im plicated in ARVC. In summary, although additional studies are required to fully establish its clinical significance, the c.523+2T>C variant is likely pathogenic . ACMG/AMP Criteria applied: PM2; PVS1_Moderate; PS4_Moderate.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided5not provided4not provided

Last Updated: Nov 27, 2021

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