ClinVar Genomic variation as it relates to human health
NM_001943.5(DSG2):c.473T>G (p.Val158Gly)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001943.5(DSG2):c.473T>G (p.Val158Gly)
Variation ID: 44319 Accession: VCV000044319.60
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 18q12.1 18: 31521193 (GRCh38) [ NCBI UCSC ] 18: 29101156 (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 Dec 6, 2014 Aug 4, 2024 May 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001943.5:c.473T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001934.2:p.Val158Gly missense NC_000018.10:g.31521193T>G NC_000018.9:g.29101156T>G NG_007072.3:g.27952T>G LRG_397:g.27952T>G LRG_397t1:c.473T>G Q14126:p.Val158Gly - Protein change
- V158G
- Other names
- p.V158G:GTG>GGG
- Canonical SPDI
- NC_000018.10:31521192:T:G
-
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.
-
0.00140 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00140
1000 Genomes Project 30x 0.00141
Trans-Omics for Precision Medicine (TOPMed) 0.00498
Exome Aggregation Consortium (ExAC) 0.00538
The Genome Aggregation Database (gnomAD) 0.00550
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00617
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 |
1110 | 1917 |
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/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Oct 11, 2017 | RCV000037307.29 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000148470.10 | |
Likely benign (1) |
criteria provided, single submitter
|
Mar 11, 2015 | RCV000211473.3 | |
Benign (1) |
criteria provided, single submitter
|
Nov 20, 2015 | RCV000250164.4 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
May 1, 2024 | RCV000589551.26 | |
Benign (1) |
criteria provided, single submitter
|
Apr 9, 2018 | RCV000771099.3 | |
Benign (1) |
criteria provided, single submitter
|
Jun 11, 2019 | RCV000852740.2 | |
Benign (1) |
criteria provided, single submitter
|
Feb 1, 2024 | RCV001081252.9 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 22, 2022 | RCV002490506.2 |
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
(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: SCV000051527.2 First in ClinVar: Jun 08, 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: 11
|
|
Likely benign
(Mar 11, 2015)
|
criteria provided, single submitter
Method: research
|
Arrhythmogenic right ventricular dysplasia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: CSER - NEXT Medicine variant annotation
Accession: SCV000212209.1 First in ClinVar: May 21, 2016 Last updated: May 21, 2016 |
Indication for testing: adults with personal and/or family history of colorectal cancer and/or polyps
|
|
Benign
(Jan 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697889.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: This c.473T>G variant affects a conserved nucleotide, resulting in amino acid change from Val to Gly. 3/4 in-silico tools predict this variant to … (more)
Variant summary: This c.473T>G variant affects a conserved nucleotide, resulting in amino acid change from Val to Gly. 3/4 in-silico tools predict this variant to be damaging; however, results from in silico prediction are not definitive. This variant was found in 674/124228 control chromosomes including the broad and large populations from ExAC at a frequency of 0.0054255, which is more than 216 times greater than the maximal expected frequency of a pathogenic allele (0.000025) in this gene, suggesting this variant is benign. In addition, three homozygotes have also been reported from the European (Non-Finnish) population from ExAC, further supporting its benign outcome for the dominant disorders associated with this gene. This variant has been reported in literature in many patients with varying cardiological phenotypes, namely ARVD, DCM, Brugada Syndrome, and Arrhythmia; however, without strong evidence for causality. Rather, this variant was reported to co-occur with DSG2 R46Q and PKP2 p.L452X, supporting for a benign outcome. The variant has also been reported in an unaffected relative of an ARVD family, suggesting a lack of cosegregation (Syrris_2007). Multiple clinical labs have classified this variant as benign/likely benign. Taken together, this variant has been classified as Benign. (less)
|
|
Benign
(May 01, 2012)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000168233.10
First in ClinVar: Jun 23, 2014 Last updated: Apr 09, 2018 |
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
(Oct 11, 2017)
|
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: SCV000060964.5
First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018 |
Comment:
p.Val158Gly in exon 5 of DSG2: This variant is not expected to have clinical sig nificance because it is not located within the splice consensus … (more)
p.Val158Gly in exon 5 of DSG2: This variant is not expected to have clinical sig nificance because it is not located within the splice consensus sequence and has been identified in 0.8% (212/25742) of Finnish chromosomes by the Genome Aggreg ation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs191143292). AC MG/AMP Criteria applied: BA1 (Richards 2015). (less)
Number of individuals with the variant: 22
|
|
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: SCV000262068.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
|
|
Benign
(Nov 09, 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: SCV000883745.5
First in ClinVar: Mar 17, 2018 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: SCV004819447.1
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: 1326
|
|
Likely benign
(May 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002498359.16
First in ClinVar: Apr 08, 2022 Last updated: Aug 04, 2024 |
Comment:
DSG2: BP4, BS2
Number of individuals with the variant: 9
|
|
Likely benign
(Mar 18, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000231023.5
First in ClinVar: Jun 28, 2015 Last updated: Sep 22, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Benign
(Apr 09, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000902737.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Arrhythmogenic right ventricular cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV000987331.1
First in ClinVar: Sep 09, 2019 Last updated: Sep 09, 2019 |
|
|
Benign
(Jun 11, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Dilated cardiomyopathy
Cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995456.1
First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019 |
Number of individuals with the variant: 3
|
|
Likely benign
(Apr 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Arrhythmogenic right ventricular dysplasia 10
Dilated cardiomyopathy 1BB
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002796082.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Benign
(Nov 20, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000318919.7
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)
|
|
Likely benign
(Jun 01, 2014)
|
no assertion criteria provided
Method: research
|
Cardiomyopathy, arrhythmogenic right ventricular
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190170.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
|
|
|
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: SCV001923770.1 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
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929204.1 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
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953280.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 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: SCV001974892.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001739838.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
click to load more click to collapse |
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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Genetic Analysis of Arrhythmogenic Diseases in the Era of NGS: The Complexity of Clinical Decision-Making in Brugada Syndrome. | Allegue C | PloS one | 2015 | PMID: 26230511 |
Actionable exomic incidental findings in 6503 participants: challenges of variant classification. | Amendola LM | Genome research | 2015 | PMID: 25637381 |
Assessment of HaloPlex amplification for sequence capture and massively parallel sequencing of arrhythmogenic right ventricular cardiomyopathy-associated genes. | Gréen A | The Journal of molecular diagnostics : JMD | 2015 | PMID: 25445213 |
Potential genetic predisposition for anthracycline-associated cardiomyopathy in families with dilated cardiomyopathy. | Wasielewski M | Open heart | 2014 | PMID: 25332820 |
Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis. | Rasmussen TB | Circulation. Cardiovascular genetics | 2014 | PMID: 24704780 |
Personalized genomic disease risk of volunteers. | Gonzalez-Garay ML | Proceedings of the National Academy of Sciences of the United States of America | 2013 | PMID: 24082139 |
Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
Risk stratification in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. | Bhonsale A | Circulation. Arrhythmia and electrophysiology | 2013 | PMID: 23671136 |
New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. | Andreasen C | European journal of human genetics : EJHG | 2013 | PMID: 23299917 |
Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study. | Cox MG | Circulation | 2011 | PMID: 21606396 |
Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria. | Quarta G | Circulation | 2011 | PMID: 21606390 |
Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy. | Lahtinen AM | Heart rhythm | 2011 | PMID: 21397041 |
Shared desmosome gene findings in early and late onset arrhythmogenic right ventricular dysplasia/cardiomyopathy. | Tan BY | Journal of cardiovascular translational research | 2010 | PMID: 20857253 |
Assessment of inflammation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. | Campian ME | European journal of nuclear medicine and molecular imaging | 2010 | PMID: 20603720 |
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 |
A genetic variants database for arrhythmogenic right ventricular dysplasia/cardiomyopathy. | van der Zwaag PA | Human mutation | 2009 | PMID: 19569224 |
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 |
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 |
Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease. | Syrris P | European heart journal | 2007 | PMID: 17105751 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DSG2 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs191143292 ...
HelpRecord last updated Sep 29, 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.