NM_001943.5(DSG2):c.2257del (p.Ala753fs) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 10, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000706687.8

Allele description [Variation Report for NM_001943.5(DSG2):c.2257del (p.Ala753fs)]

NM_001943.5(DSG2):c.2257del (p.Ala753fs)

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.2257del (p.Ala753fs)

HGVS:

NC_000018.10:g.31542775del
NG_007072.3:g.49534del
NM_001943.5:c.2257delMANE SELECT
NP_001934.2:p.Ala753fs
LRG_397t1:c.2257del
LRG_397:g.49534del
NC_000018.9:g.29122735del
NC_000018.9:g.29122738del
NM_001943.3:c.2257delG

Protein change:

A753fs

Links:

dbSNP: rs1567933176

NCBI 1000 Genomes Browser:

rs1567933176

Molecular consequence:

NM_001943.5:c.2257del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 10
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular cardiomyopathy, type 10; Arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 10; See all synonyms [MedGen]
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
SCV000835754	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 10, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20864495, 21397041, 23381804, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000835754

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 10, 2022)

germline

clinical testing

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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000835754.5

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

Description

For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 582579). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala753Leufs*15) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 366 amino acid(s) of the DSG2 protein.

#	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: Sep 29, 2024

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