This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ClinVar Genomic variation as it relates to human health
NM_001943.5(DSG2):c.2137G>A (p.Glu713Lys)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(18)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Benign/Likely benign
18
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001943.5(DSG2):c.2137G>A (p.Glu713Lys)
Variation ID: 44295 Accession: VCV000044295.42
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 18q12.1 18: 31542655 (GRCh38) [ NCBI UCSC ] 18: 29122618 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 14, 2015 Sep 29, 2024 Feb 5, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001943.5:c.2137G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001934.2:p.Glu713Lys missense NC_000018.10:g.31542655G>A NC_000018.9:g.29122618G>A NG_007072.3:g.49414G>A LRG_397:g.49414G>A LRG_397t1:c.2137G>A Q14126:p.Glu713Lys - Protein change
- E713K
- Other names
-
p.E713K:GAG>AAG
- Canonical SPDI
- NC_000018.10:31542654:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.02596 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.05186
The Genome Aggregation Database (gnomAD), exomes 0.05294
1000 Genomes Project 30x 0.02483
1000 Genomes Project 0.02596
Trans-Omics for Precision Medicine (TOPMed) 0.04746
The Genome Aggregation Database (gnomAD) 0.05477
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.05843
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| DSG2 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1115 | 1922 | |
| DSG2-AS1 | - | - | - | GRCh38 | - | 698 |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign (9) |
criteria provided, multiple submitters, no conflicts
|
Jul 4, 2019 | RCV000037280.30 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000172746.13 | |
| Benign (1) |
criteria provided, single submitter
|
Jun 23, 2015 | RCV000246238.11 | |
| Benign (2) |
criteria provided, single submitter
|
Apr 8, 2018 | RCV000776008.12 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV001094500.19 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 29, 2023 | RCV001811256.17 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Mar 22, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000233467.10
First in ClinVar: Jul 05, 2015 Last updated: Dec 06, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
|
Benign
(Nov 11, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000337025.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Benign
(Jun 03, 2011)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000060937.5
First in ClinVar: May 03, 2013 Last updated: Dec 06, 2016 |
Comment:
The Glu713Lys variant in DSG2 is a common variant with allele frequencies rangin g from 2-8% in various control cohorts (dbSNP-rs7924116, Biedermann 2005, Basso 2006, … (more)
The Glu713Lys variant in DSG2 is a common variant with allele frequencies rangin g from 2-8% in various control cohorts (dbSNP-rs7924116, Biedermann 2005, Basso 2006, Posche 2008, Milting 2008, Drudge 2008, Kauke 2010). At this frequency thi s variant is highly unlikley to cause disease when present in isoaltion but a mo difying role cannot be excluded. Please note that it has also been referred to i n the literature as Glu712Lys. (less)
Number of individuals with the variant: 240
|
|
|
Benign
(Jun 23, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000317544.7
First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Benign
(Jun 24, 2013)
|
criteria provided, single submitter
Method: research
|
Cardiomyopathy, arrhythmogenic right ventricular
Affected status: unknown
Allele origin:
unknown
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000051531.2 First in ClinVar: Jun 04, 2015 Last updated: Sep 14, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
|
Number of individuals with the variant: 113
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000308553.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Apr 08, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000910545.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Arrhythmogenic right ventricular dysplasia 10
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000408240.3
First in ClinVar: Sep 14, 2015 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Benign
(Jul 04, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433059.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Arrhythmogenic right ventricular dysplasia 10
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001729153.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000883741.7
First in ClinVar: Feb 18, 2019 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Arrhythmogenic right ventricular cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004821758.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 13415
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005215247.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927182.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001971159.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978714.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979040.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
|
Benign
(Sep 23, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Cohesion Phenomics
Accession: SCV003802739.1
First in ClinVar: Feb 18, 2023 Last updated: Feb 18, 2023 |
|
|
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Comment:
Comment:
The Glu713Lys variant in DSG2 is a common variant with allele frequencies rangin g from 2-8% in various control cohorts (dbSNP-rs7924116, Biedermann 2005, Basso 2006, Posche 2008, Milting 2008, Drudge 2008, Kauke 2010). At this frequency thi s variant is highly unlikley to cause disease when present in isoaltion but a mo difying role cannot be excluded. Please note that it has also been referred to i n the literature as Glu712Lys.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Germline Functional Evidence
| 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. |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
The Glu713Lys variant in DSG2 is a common variant with allele frequencies rangin g from 2-8% in various control cohorts (dbSNP-rs7924116, Biedermann 2005, Basso 2006, Posche 2008, Milting 2008, Drudge 2008, Kauke 2010). At this frequency thi s variant is highly unlikley to cause disease when present in isoaltion but a mo difying role cannot be excluded. Please note that it has also been referred to i n the literature as Glu712Lys.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. | Klauke B | Human molecular genetics | 2010 | PMID: 20829228 |
| Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia. | Barahona-Dussault C | Clinical genetics | 2010 | PMID: 19863551 |
| Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. | den Haan AD | Circulation. Cardiovascular genetics | 2009 | PMID: 20031617 |
| Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study. | Bhuiyan ZA | Circulation. Cardiovascular genetics | 2009 | PMID: 20031616 |
| Variations in DSG2: V56M, V158G and V920G are not pathogenic for arrhythmogenic right ventricular dysplasia/cardiomyopathy. | Posch MG | Nature clinical practice. Cardiovascular medicine | 2008 | PMID: 19039334 |
| Molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. | Milting H | Nature clinical practice. Cardiovascular medicine | 2008 | PMID: 18813333 |
| A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy. | Posch MG | Molecular genetics and metabolism | 2008 | PMID: 18678517 |
| Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. | Awad MM | Nature clinical practice. Cardiovascular medicine | 2008 | PMID: 18382419 |
| Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies. | Basso C | European heart journal | 2006 | PMID: 16774985 |
| Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer. | Biedermann K | The Journal of pathology | 2005 | PMID: 16025435 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DSG2 | - | - | - | - |
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Text-mined citations for rs79241126 ...
HelpThese 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 Nov 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.