GeneBe

DSC2

desmocollin 2, the group of Desmosomal cadherins

Basic information

Region (hg38): 18:31058545-31102600

Previous symbols: [ "DSC3" ]

Links

ENSG00000134755 ∙ NCBI:1824 ∙ OMIM:125645 ∙ HGNC:3036 ∙ Uniprot:Q02487 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • arrhythmogenic right ventricular dysplasia 11 (Strong), mode of inheritance: AR
  • arrhythmogenic right ventricular dysplasia 11 (Definitive), mode of inheritance: Semidominant
  • colorectal adenoma (Limited), mode of inheritance: AD
  • 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
  • familial isolated arrhythmogenic right ventricular dysplasia (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Arrhythmogenic right ventricular dysplasia, familial, 11AD/ARCardiovascularIndividuals 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 transplantationCardiovascular; Dermatologic12392835; 17033975; 17186466; 18957847; 20197793; 20301310

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DSC2 gene.

  • Arrhythmogenic_right_ventricular_dysplasia_11 (1147 variants)
  • Cardiomyopathy (644 variants)
  • Familial_isolated_arrhythmogenic_right_ventricular_dysplasia (589 variants)
  • Cardiovascular_phenotype (553 variants)
  • not_provided (344 variants)
  • not_specified (195 variants)
  • Arrhythmogenic_right_ventricular_cardiomyopathy (33 variants)
  • DSC2-related_disorder (30 variants)
  • Primary_dilated_cardiomyopathy (6 variants)
  • Hypertrophic_cardiomyopathy (5 variants)
  • Primary_familial_hypertrophic_cardiomyopathy (4 variants)
  • Long_QT_syndrome (3 variants)
  • Dilated_cardiomyopathy_1A (2 variants)
  • Arrhythmogenic_right_ventricular_dysplasia_1 (2 variants)
  • ARRHYTHMOGENIC_RIGHT_VENTRICULAR_DYSPLASIA,_FAMILIAL,_11,_WITH_OR_WITHOUT_MILD_PALMOPLANTAR_KERATODERMA (1 variants)
  • Sudden_unexplained_death (1 variants)
  • Left_ventricular_hypertrophy (1 variants)
  • Arrhythmogenic_right_ventricular_dysplasia,_familial,_11,_with_mild_palmoplantar_keratoderma_and_woolly_hair (1 variants)
  • See_cases (1 variants)
  • Arrhythmogenic_right_ventricular_dysplasia_9 (1 variants)
  • Dilated_cardiomyopathy_1S (1 variants)
  • Primary_familial_dilated_cardiomyopathy (1 variants)
  • Cardiac_arrest (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. These statistics are base on transcript: NM_000024422.6. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
13
clinvar
365
clinvar
5
clinvar
 383
missense
3
clinvar
3
clinvar
881
clinvar
85
clinvar
8
clinvar
 980
nonsense
13
clinvar
19
clinvar
11
clinvar
 43
start loss
3
 3
frameshift
37
clinvar
24
clinvar
36
clinvar
1
clinvar
2
clinvar
 100
splice donor/acceptor (+/-2bp)
28
clinvar
10
clinvar
 38
Total 53 74 954 451 15

Highest pathogenic variant AF is 0.00002603024

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DSC2protein_codingprotein_codingENST00000280904 1636439
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
5.17e-81.001256990491257480.000195
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.3734584810.9520.00002475879
Missense in Polyphen153185.410.825182390
Synonymous-0.1871821791.020.000009821772
Loss of Function3.131940.50.4690.00000191531

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001480.000148
Ashkenazi Jewish0.00009930.0000992
East Asian0.0002720.000272
Finnish0.000.00
European (Non-Finnish)0.0002640.000264
Middle Eastern0.0002720.000272
South Asian0.0002290.000229
Other0.0003260.000326

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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