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NM_001943.5(DSG2):c.3039C>A (p.Tyr1013Ter)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Sep 23, 2021)
Last evaluated:
Nov 17, 2020
Accession:
VCV000392196.7
Variation ID:
392196
Description:
single nucleotide variant
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NM_001943.5(DSG2):c.3039C>A (p.Tyr1013Ter)

Allele ID
378974
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
18q12.1
Genomic location
18: 31546425 (GRCh38) GRCh38 UCSC
18: 29126388 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_397:g.53184C>A
LRG_397t1:c.3039C>A
NC_000018.10:g.31546425C>A
... more HGVS
Protein change
Y1013*
Other names
-
Canonical SPDI
NC_000018.10:31546424:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00040 (A)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
1000 Genomes Project 0.00040
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA047781
dbSNP: rs539821357
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Oct 16, 2019 RCV000769518.2
Uncertain significance 1 criteria provided, single submitter Nov 17, 2020 RCV000431080.2
Pathogenic 1 criteria provided, single submitter Oct 10, 2020 RCV000642320.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
DSG2 Little evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
638 1094
DSG2-AS1 - - - GRCh38 - 435

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 10, 2020)
criteria provided, single submitter
Method: clinical testing
Arrhythmogenic right ventricular cardiomyopathy, type 10
Allele origin: germline
Invitae
Accession: SCV000763989.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change results in a premature translational stop signal in the DSG2 gene (p.Tyr1013*). While this is not anticipated to result in nonsense mediated … (more)
Uncertain significance
(Nov 17, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000535422.5
Submitted: (Sep 23, 2021)
Evidence details
Comment:
Nonsense variant predicted to result in protein truncation as the last 106 amino acids are lost, although loss-of-function variants have not been reported downstream of … (more)
Uncertain significance
(Nov 30, 2016)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Allele origin: germline
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000900913.1
Submitted: (Apr 30, 2018)
Evidence details
Uncertain significance
(Oct 16, 2019)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Allele origin: germline
Color Health, Inc
Accession: SCV001343658.1
Submitted: (May 19, 2020)
Comment:
This variant changes 1 nucleotide in exon 15 of the DSG2 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Mutated desmoglein-2 proteins are incorporated into desmosomes and exhibit dominant-negative effects in arrhythmogenic right ventricular cardiomyopathy. Rasmussen TB Human mutation 2013 PMID: 23381804
Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy. Lahtinen AM Heart rhythm 2011 PMID: 21397041
Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy. Christensen AH Journal of medical genetics 2010 PMID: 20864495

Text-mined citations for rs539821357...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2021