DSG2
desmoglein 2, the group of Desmosomal cadherins
Basic information
Region (hg38): 18:31497624-31551351
Links
Phenotypes
GenCC
Source:
- arrhythmogenic right ventricular dysplasia 10 (Definitive), mode of inheritance: AD
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- arrhythmogenic right ventricular dysplasia 10 (Strong), mode of inheritance: AD
- dilated cardiomyopathy 1BB (Limited), mode of inheritance: AR
- dilated cardiomyopathy 1BB (Limited), mode of inheritance: AR
- arrhythmogenic right ventricular dysplasia 10 (Definitive), mode of inheritance: AD
- arrhythmogenic right ventricular dysplasia 10 (Definitive), mode of inheritance: AR
- arrhythmogenic right ventricular dysplasia 10 (Moderate), mode of inheritance: AR
- dilated cardiomyopathy (Limited), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardiomyopathy, dilated, 1BB; Arrhythmogenic right ventricular dysplasia, familial, 10 | AD | Cardiovascular | In Arrhythmogenic right ventricular dysplasia, familial, 10, individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation; In Dilated cardiomyopathy; surveillance (eg, with echocardiography) may allow early detection of sequelae and medical management, which may decreased morbidity and mortality; Cardiac transplantation has been described | Cardiovascular | 16773573; 16505173; 17105751; 18678517; 20301310 |
ClinVar
This is a list of variants' phenotypes submitted to
- Arrhythmogenic right ventricular dysplasia 10 (31 variants)
- not provided (5 variants)
- Cardiovascular phenotype (4 variants)
- Arrhythmogenic right ventricular cardiomyopathy (1 variants)
- Arrhythmogenic right ventricular dysplasia 10;Dilated cardiomyopathy 1BB (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSG2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 326 | 342 | |||
| missense | 842 | 29 | 881 | |||
| nonsense | 12 | 12 | 29 | |||
| start loss | 3 | |||||
| frameshift | 22 | 27 | 28 | 77 | ||
| inframe indel | 21 | 21 | ||||
| splice donor/acceptor (+/-2bp) | 20 | 26 | ||||
| splice region | 29 | 35 | 64 | |||
| non coding | 62 | 117 | 41 | 220 | ||
| Total | 36 | 63 | 976 | 472 | 52 |
Highest pathogenic variant AF is 0.0000200
Variants in DSG2
This is a list of pathogenic ClinVar variants found in the DSG2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 18-31498074-G-A | Arrhythmogenic right ventricular dysplasia 10 | Uncertain significance (Jan 13, 2018) | ||
| 18-31498096-G-A | Arrhythmogenic right ventricular dysplasia 10 | Uncertain significance (Jan 13, 2018) | ||
| 18-31498097-G-GC | Dilated Cardiomyopathy, Dominant • Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Jun 14, 2016) | ||
| 18-31498108-G-A | Arrhythmogenic right ventricular dysplasia 10 | Uncertain significance (Jan 13, 2018) | ||
| 18-31498117-A-T | Arrhythmogenic right ventricular dysplasia 10 | Uncertain significance (Jan 12, 2018) | ||
| 18-31498158-G-C | Arrhythmogenic right ventricular dysplasia 10 | Benign/Likely benign (Jan 12, 2018) | ||
| 18-31498173-C-G | Arrhythmogenic right ventricular dysplasia 10 | Conflicting classifications of pathogenicity (Dec 01, 2022) | ||
| 18-31498197-G-C | Arrhythmogenic right ventricular dysplasia 10 | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 18-31498202-AGGCGGCGGCGCGGAGCGGTGC-A | Cardiomyopathy | Uncertain significance (Oct 14, 2016) | ||
| 18-31498208-C-A | Arrhythmogenic right ventricular cardiomyopathy • Dilated Cardiomyopathy, Dominant | Uncertain significance (Jun 14, 2016) | ||
| 18-31498215-G-C | Benign (Mar 03, 2015) | |||
| 18-31498219-G-A | Arrhythmogenic right ventricular dysplasia 10 • Arrhythmogenic right ventricular dysplasia 10;Dilated cardiomyopathy 1BB | Uncertain significance (Jul 14, 2021) | ||
| 18-31498226-CGGCGGGAGGCGGAGGCGAGGGTGCGAT-C | Uncertain significance (Dec 01, 2020) | |||
| 18-31498230-G-A | not specified | Likely benign (Oct 26, 2015) | ||
| 18-31498234-G-GGCGGAGGCGAGGGTGCGATGGC | Cardiovascular phenotype | Uncertain significance (May 01, 2023) | ||
| 18-31498236-C-G | not specified | Likely benign (Aug 17, 2016) | ||
| 18-31498237-G-A | not specified • Cardiomyopathy | Uncertain significance (Dec 23, 2019) | ||
| 18-31498238-G-GAGGCGA | Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Aug 13, 2024) | ||
| 18-31498240-G-A | Cardiomyopathy • Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Mar 24, 2024) | ||
| 18-31498241-G-A | not specified • Cardiomyopathy | Uncertain significance (Mar 16, 2023) | ||
| 18-31498244-AG-A | Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Feb 05, 2024) | ||
| 18-31498248-T-G | Dilated Cardiomyopathy, Dominant • Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Jun 14, 2016) | ||
| 18-31498249-G-A | Cardiomyopathy | Uncertain significance (Feb 23, 2022) | ||
| 18-31498250-C-T | Cardiomyopathy | Uncertain significance (Dec 21, 2020) | ||
| 18-31498251-G-A | Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (May 16, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DSG2 | protein_coding | protein_coding | ENST00000261590 | 15 | 50966 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.79e-10 | 0.995 | 124699 | 0 | 99 | 124798 | 0.000397 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.296 | 567 | 587 | 0.966 | 0.0000299 | 7316 |
| Missense in Polyphen | 188 | 201.62 | 0.93244 | 2621 | ||
| Synonymous | 0.673 | 207 | 220 | 0.942 | 0.0000128 | 2243 |
| Loss of Function | 2.61 | 22 | 39.7 | 0.553 | 0.00000186 | 532 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000615 | 0.000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00128 | 0.00128 |
| Finnish | 0.000186 | 0.000186 |
| European (Non-Finnish) | 0.000365 | 0.000353 |
| Middle Eastern | 0.00128 | 0.00128 |
| South Asian | 0.000436 | 0.000425 |
| Other | 0.000664 | 0.000660 |
dbNSFP
Source:
- Function
- FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.;
- Disease
- DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 10 (ARVD10) [MIM:610193]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. {ECO:0000269|PubMed:16773573, ECO:0000269|PubMed:19863551, ECO:0000269|PubMed:20031617, ECO:0000269|PubMed:21062920}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1BB (CMD1BB) [MIM:612877]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:18678517}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);miR-targeted genes in muscle cell - TarBase;Arrhythmogenic Right Ventricular Cardiomyopathy;Keratinization;Developmental Biology;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Apoptotic execution phase;Apoptosis;Programmed Cell Death;EGFR1;Formation of the cornified envelope
(Consensus)
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- loftool
- 0.783
- rvis_EVS
- 2.3
- rvis_percentile_EVS
- 98.32
Haploinsufficiency Scores
- pHI
- 0.435
- hipred
- Y
- hipred_score
- 0.687
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.507
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dsg2
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype;
Zebrafish Information Network
- Gene name
- dsg2.1
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- curved
Gene ontology
- Biological process
- desmosome organization;Purkinje myocyte development;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;keratinization;response to progesterone;maternal process involved in female pregnancy;cornification;bundle of His cell-Purkinje myocyte adhesion involved in cell communication;regulation of heart rate by cardiac conduction;regulation of ventricular cardiac muscle cell action potential
- Cellular component
- cornified envelope;plasma membrane;cell-cell junction;cell surface;intercalated disc;integral component of membrane;apical plasma membrane;lateral plasma membrane;cell junction;desmosome;intracellular membrane-bounded organelle;extracellular exosome
- Molecular function
- calcium ion binding;cell adhesion molecule binding;cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication