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NM_001943.5(DSG2):c.545A>G (p.Asn182Ser)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(3);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Sep 20, 2021)
Last evaluated:
Mar 9, 2021
Accession:
VCV000044323.10
Variation ID:
44323
Description:
single nucleotide variant
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NM_001943.5(DSG2):c.545A>G (p.Asn182Ser)

Allele ID
53490
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
18q12.1
Genomic location
18: 31522104 (GRCh38) GRCh38 UCSC
18: 29102067 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000018.10:g.31522104A>G
NC_000018.9:g.29102067A>G
NG_007072.3:g.28863A>G
... more HGVS
Protein change
N182S
Other names
-
Canonical SPDI
NC_000018.10:31522103:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (G)

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00025
The Genome Aggregation Database (gnomAD) 0.00025
Trans-Omics for Precision Medicine (TOPMed) 0.00014
The Genome Aggregation Database (gnomAD), exomes 0.00004
Exome Aggregation Consortium (ExAC) 0.00005
1000 Genomes Project 0.00020
Links
ClinGen: CA022181
dbSNP: rs368512832
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 criteria provided, multiple submitters, no conflicts Nov 25, 2019 RCV000037311.7
Uncertain significance 1 criteria provided, single submitter Jun 29, 2020 RCV000226293.7
Uncertain significance 1 criteria provided, single submitter Aug 27, 2020 RCV000620980.2
Uncertain significance 2 criteria provided, single submitter Mar 9, 2021 RCV000766579.3
Likely benign 1 criteria provided, single submitter Jul 29, 2019 RCV001189713.1
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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

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Apr 13, 2015)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000060968.5
Submitted: (Mar 21, 2019)
Evidence details
Comment:
p.Asn182Ser in exon 6 of DSG2: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including … (more)
Uncertain significance
(Aug 27, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737989.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (4)
Comment:
The p.N182S variant (also known as c.545A>G), located in coding exon 6 of the DSG2 gene, results from an A to G substitution at nucleotide … (more)
Uncertain significance
(Mar 09, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000518616.5
Submitted: (Sep 20, 2021)
Evidence details
Comment:
Reported in association with DCM, including an African American female with infantile-onset DCM who harbored additional disease-related variants (Pugh et al., 2014; Walsh et al., … (more)
Likely benign
(Jul 29, 2019)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Allele origin: germline
Color Health, Inc
Accession: SCV001357063.1
Submitted: (May 19, 2020)
Evidence details
Likely benign
(Nov 25, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361557.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: DSG2 c.545A>G (p.Asn182Ser) results in a conservative amino acid change located in the second cadherin repeat (IPR002126) of the encoded protein sequence, which … (more)
Uncertain significance
(Jun 29, 2020)
criteria provided, single submitter
Method: clinical testing
Arrhythmogenic right ventricular cardiomyopathy, type 10
Allele origin: germline
Invitae
Accession: SCV000287245.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces asparagine with serine at codon 182 of the DSG2 protein (p.Asn182Ser). The asparagine residue is moderately conserved and there is a … (more)
Uncertain significance
(May 13, 2016)
no assertion criteria provided
Method: provider interpretation
not provided
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000924769.1
Submitted: (Aug 15, 2018)
Evidence details
Comment:
p.Asn182Ser (c.545A>G) in the DSG2 gene (NM_01943.3) We have seen this in one African-American adult with mild dilated cardiomyopathy and a family history suspicious for … (more)

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
In vitro analysis of arrhythmogenic cardiomyopathy associated desmoglein-2 (DSG2) mutations reveals diverse glycosylation patterns. Debus JD Journal of molecular and cellular cardiology 2019 PMID: 30885746
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Walsh R Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 27532257
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Lopes LR Heart (British Cardiac Society) 2015 PMID: 25351510
The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Pugh TJ Genetics in medicine : official journal of the American College of Medical Genetics 2014 PMID: 24503780
Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing. Lopes LR Journal of medical genetics 2013 PMID: 23396983

Text-mined citations for rs368512832...

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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 Sep 23, 2021