NM_001943.5(DSG2):c.2817del (p.Tyr940fs) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 8, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000699399.17

Allele description [Variation Report for NM_001943.5(DSG2):c.2817del (p.Tyr940fs)]

NM_001943.5(DSG2):c.2817del (p.Tyr940fs)

Genes:

DSG2-AS1:DSG2 antisense RNA 1 [Gene - HGNC]
DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.2817del (p.Tyr940fs)

HGVS:

NC_000018.10:g.31546203del
NG_007072.3:g.52962del
NM_001943.5:c.2817delMANE SELECT
NP_001934.2:p.Tyr940fs
LRG_397t1:c.2817del
LRG_397:g.52962del
NC_000018.9:g.29126165del
NC_000018.9:g.29126166del
NM_001943.3:c.2817delC
NM_001943.4:c.2817del

Protein change:

Y940fs

Links:

dbSNP: rs1567934773

NCBI 1000 Genomes Browser:

rs1567934773

Molecular consequence:

NM_001943.5:c.2817del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 10
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 10; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy10
Identifiers:: MONDO: MONDO:0012434; MedGen: C1857777; OMIM: 610193

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000828106	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 8, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20864495, 21397041, 23381804, 28492532
SCV001434979	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 6, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000828106

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 8, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001434979

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 6, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy.

Christensen AH, Benn M, Bundgaard H, Tybjaerg-Hansen A, Haunso S, Svendsen JH.

J Med Genet. 2010 Nov;47(11):736-44. doi: 10.1136/jmg.2010.077891. Epub 2010 Sep 23.

PubMed [citation]

PMID:: 20864495

Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy.

Lahtinen AM, Lehtonen E, Marjamaa A, Kaartinen M, Heliö T, Porthan K, Oikarinen L, Toivonen L, Swan H, Jula A, Peltonen L, Palotie A, Salomaa V, Kontula K.

Heart Rhythm. 2011 Aug;8(8):1214-21. doi: 10.1016/j.hrthm.2011.03.015. Epub 2011 Mar 10.

PubMed [citation]

PMID:: 21397041

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000828106.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant disrupts a region of the DSG2 protein in which other variant(s) (p.Glu1020Alafs*18) have been determined to be pathogenic (PMID: 20864495, 21397041, 23381804). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Tyr940Metfs*12) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 179 amino acid(s) of the DSG2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 576810). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001434979.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The frameshift variant, c.2817delC (p.Tyr940Metfs*12) in the DSG2 gene is predicted to introduce a premature translation termination codon. It has not been seen in the general population according to the gnomAD database. Loss of function could be the mechanism for DSG2 protein (PMID 23911551, 23381804). Therefore, this variant is classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 28, 2025

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