DSC2

desmocollin 2, the group of Desmosomal cadherins

Basic information

Region (hg38): 18:31058839-31102522

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

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 ClinVar and linked to the DSC2 gene.

• Arrhythmogenic right ventricular dysplasia 11 (927 variants)
• Cardiomyopathy (598 variants)
• Cardiovascular phenotype (349 variants)
• not provided (294 variants)
• not specified (179 variants)
• Arrhythmogenic right ventricular cardiomyopathy (46 variants)
• Inborn genetic diseases (17 variants)
• Primary dilated cardiomyopathy (6 variants)
• Hypertrophic cardiomyopathy (5 variants)
• Familial isolated arrhythmogenic right ventricular dysplasia (4 variants)
• Primary familial hypertrophic cardiomyopathy (4 variants)
• DSC2-related condition (2 variants)
• Arrhythmogenic right ventricular dysplasia 1 (2 variants)
• Long QT syndrome (2 variants)
• Dilated cardiomyopathy 1A (2 variants)
• Aborted sudden cardiac death (1 variants)
• Cardiac arrest (1 variants)
• Dilated cardiomyopathy 1S (1 variants)
• Primary familial dilated cardiomyopathy (1 variants)
• ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 11, WITH OR WITHOUT MILD PALMOPLANTAR KERATODERMA (1 variants)
• See cases (1 variants)
• Pigmented nodular adrenocortical disease, primary, 2 (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			6	254	1	261
missense		1	607	13	3	624
nonsense	11	5	8			24
start loss			1			1
frameshift	23	12	17	1	2	55
inframe indel			9			9
splice donor/acceptor (+/-2bp)		14	7			21
splice region			26	30		56
non coding			64	123	38	225
Total	34	32	719	391	44

Highest pathogenic variant AF is 0.00000658

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: gnomAD

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: 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

	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