DSG2

desmoglein 2, the group of Desmosomal cadherins

Basic information

Region (hg38): 18:31498176-31549008

Links

ENSG00000046604 ∙ NCBI:1829 ∙ OMIM:125671 ∙ HGNC:3049 ∙ Uniprot:Q14126 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the DSG2 gene.

• Arrhythmogenic right ventricular dysplasia 10 (1063 variants)
• Cardiomyopathy (714 variants)
• Cardiovascular phenotype (420 variants)
• not provided (349 variants)
• not specified (204 variants)
• Arrhythmogenic right ventricular dysplasia 10;Dilated cardiomyopathy 1BB (75 variants)
• Arrhythmogenic right ventricular cardiomyopathy (72 variants)
• Dilated cardiomyopathy 1BB;Arrhythmogenic right ventricular dysplasia 10 (30 variants)
• Dilated Cardiomyopathy, Dominant (25 variants)
• Inborn genetic diseases (16 variants)
• Primary dilated cardiomyopathy (7 variants)
• Dilated cardiomyopathy 1BB (6 variants)
• DSG2-related condition (6 variants)
• Primary familial hypertrophic cardiomyopathy (5 variants)
• Long QT syndrome (4 variants)
• Hypertrophic cardiomyopathy (4 variants)
• Arrhythmogenic right ventricular dysplasia 1 (3 variants)
• Cardiac arrest (3 variants)
• Primary familial dilated cardiomyopathy (2 variants)
• Arrhythmogenic right ventricular dysplasia 9 (2 variants)
• Cardiomyopathy;Restrictive cardiomyopathy (2 variants)
• Cardiac arrhythmia (1 variants)
• Familial isolated dilated cardiomyopathy (1 variants)
• Ventricular fibrillation (1 variants)
• Intellectual disability (1 variants)
• Cardiomyopathy;Systolic heart failure (1 variants)
• Arrhythmogenic right ventricular cardiomyopathy;Cardiomyopathy (1 variants)
• Primary dilated cardiomyopathy;Cardiomyopathy (1 variants)
• Sudden cardiac death (1 variants)
• Conduction disorder of the heart (1 variants)
• Catecholaminergic polymorphic ventricular tachycardia 1 (1 variants)
• Left ventricular noncompaction cardiomyopathy (1 variants)
• Dilated cardiomyopathy 1A (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			3	280	6	289
missense	1	4	716	26	5	752
nonsense	11	12	4			27
start loss		1	3			4
frameshift	23	27	21			71
inframe indel			19			19
splice donor/acceptor (+/-2bp)	1	22	3			26
splice region			24	33		57
non coding			59	98	41	198
Total	36	66	828	404	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
18-31498197-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)
18-31498240-G-A		Cardiomyopathy	Uncertain significance (Dec 18, 2019)
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)
18-31498251-G-C		Cardiomyopathy • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jul 26, 2023)
18-31498252-A-C		Cardiomyopathy	Uncertain significance (May 03, 2021)
18-31498252-A-T		Cardiomyopathy	Uncertain significance (Oct 07, 2020)
18-31498254-G-A		Arrhythmogenic right ventricular dysplasia 10 • Arrhythmogenic right ventricular cardiomyopathy	Conflicting classifications of pathogenicity (Jan 17, 2024)
18-31498257-G-A		not specified • Cardiovascular phenotype • Arrhythmogenic right ventricular dysplasia 10 • Cardiomyopathy • DSG2-related disorder • Arrhythmogenic right ventricular cardiomyopathy	Benign/Likely benign (Feb 05, 2024)
18-31498257-G-T		Cardiomyopathy	Likely benign (Jul 13, 2020)
18-31498258-C-G		Arrhythmogenic right ventricular dysplasia 10	Uncertain significance (Nov 14, 2023)
18-31498257-G-GCGGAGGCGAGGGTGCGATGGCA		Arrhythmogenic right ventricular dysplasia 10	Pathogenic (Jan 14, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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