DSC2
Basic information
Region (hg38): 18:31058545-31102600
Previous symbols: [ "DSC3" ]
Links
Phenotypes
GenCC
Source:
- arrhythmogenic right ventricular dysplasia 11 (Strong), mode of inheritance: AR
- arrhythmogenic right ventricular dysplasia 11 (Definitive), mode of inheritance: Semidominant
- arrhythmogenic right ventricular dysplasia 11 (Strong), mode of inheritance: AD
- arrhythmogenic right ventricular dysplasia 11 (Limited), mode of inheritance: AR
- arrhythmogenic right ventricular dysplasia 11 (Definitive), mode of inheritance: AD
- arrhythmogenic right ventricular dysplasia 11 (Definitive), mode of inheritance: AR
- colorectal adenoma (Limited), mode of inheritance: AD
- familial isolated arrhythmogenic right ventricular dysplasia (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Arrhythmogenic right ventricular dysplasia, familial, 11 | AD/AR | Cardiovascular | 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 | Cardiovascular; Dermatologic | 12392835; 17033975; 17186466; 18957847; 20197793; 20301310 |
ClinVar
This is a list of variants' phenotypes submitted to
- Arrhythmogenic right ventricular dysplasia 11 (28 variants)
- Cardiovascular phenotype (9 variants)
- not provided (3 variants)
- Arrhythmogenic right ventricular cardiomyopathy (2 variants)
- ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 11, WITH OR WITHOUT MILD PALMOPLANTAR KERATODERMA (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSC2 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 | 291 | 296 | ||||
missense | 727 | 14 | 745 | |||
nonsense | 12 | 12 | 27 | |||
start loss | 2 | |||||
frameshift | 27 | 23 | 62 | |||
inframe indel | 12 | 12 | ||||
splice donor/acceptor (+/-2bp) | 14 | 22 | ||||
splice region | 30 | 33 | 63 | |||
non coding | 69 | 135 | 37 | 241 | ||
Total | 39 | 27 | 857 | 441 | 43 |
Highest pathogenic variant AF is 0.00000657
Variants in DSC2
This is a list of pathogenic ClinVar variants found in the DSC2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
18-31065986-T-A | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 12, 2018) | ||
18-31066043-T-G | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066088-A-G | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Apr 27, 2017) | ||
18-31066092-G-T | Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Jun 14, 2016) | ||
18-31066138-A-C | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066231-C-A | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 12, 2018) | ||
18-31066311-C-A | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066315-A-G | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066357-C-T | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066387-A-C | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 12, 2018) | ||
18-31066411-T-C | Arrhythmogenic right ventricular dysplasia 11 | Likely benign (Jan 13, 2018) | ||
18-31066474-T-A | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066540-C-G | Arrhythmogenic right ventricular dysplasia 11 | Likely benign (Jan 12, 2018) | ||
18-31066562-G-A | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066571-T-C | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066607-T-C | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 12, 2018) | ||
18-31066614-G-A | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066659-C-T | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066669-A-T | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066732-T-C | Arrhythmogenic right ventricular dysplasia 11 | Likely benign (Jan 12, 2018) | ||
18-31066778-C-T | Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Jun 14, 2016) | ||
18-31066832-C-T | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 12, 2018) | ||
18-31066857-T-C | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) | ||
18-31066889-C-A | Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Jun 14, 2016) | ||
18-31066905-T-C | Arrhythmogenic right ventricular dysplasia 11 | Uncertain significance (Jan 13, 2018) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
DSC2 | protein_coding | protein_coding | ENST00000280904 | 16 | 36439 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
5.17e-8 | 1.00 | 125699 | 0 | 49 | 125748 | 0.000195 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.373 | 458 | 481 | 0.952 | 0.0000247 | 5879 |
Missense in Polyphen | 153 | 185.41 | 0.82518 | 2390 | ||
Synonymous | -0.187 | 182 | 179 | 1.02 | 0.00000982 | 1772 |
Loss of Function | 3.13 | 19 | 40.5 | 0.469 | 0.00000191 | 531 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000148 | 0.000148 |
Ashkenazi Jewish | 0.0000993 | 0.0000992 |
East Asian | 0.000272 | 0.000272 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000264 | 0.000264 |
Middle Eastern | 0.000272 | 0.000272 |
South Asian | 0.000229 | 0.000229 |
Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.;
- Disease
- DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 11 (ARVD11) [MIM:610476]: 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:17033975, ECO:0000269|PubMed:19863551, ECO:0000269|PubMed:21062920, ECO:0000269|PubMed:28256248}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Keratinization;Developmental Biology;Formation of the cornified envelope
(Consensus)
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- loftool
- 0.741
- rvis_EVS
- -1.22
- rvis_percentile_EVS
- 5.67
Haploinsufficiency Scores
- pHI
- 0.508
- hipred
- N
- hipred_score
- 0.403
- ghis
- 0.487
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.553
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dsc2
- Phenotype
- cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype;
Gene ontology
- Biological process
- cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;cellular response to starvation;keratinization;cornification;cardiac muscle cell-cardiac muscle cell adhesion;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 adherens junction;intercalated disc;integral component of membrane;desmosome;cytoplasmic vesicle;extracellular exosome
- Molecular function
- calcium ion binding;protein binding;cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication