NM_001943.5(DSG2):c.882dup (p.Val295fs) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 22, 2024
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:: RCV001858508.11

Allele description [Variation Report for NM_001943.5(DSG2):c.882dup (p.Val295fs)]

NM_001943.5(DSG2):c.882dup (p.Val295fs)

Gene:

DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.882dup (p.Val295fs)

HGVS:

NC_000018.10:g.31524756dup
NG_007072.3:g.31515dup
NM_001943.5:c.882dupMANE SELECT
NP_001934.2:p.Val295fs
LRG_397t1:c.882dup
LRG_397:g.31515dup
NC_000018.9:g.29104715_29104716insA
NC_000018.9:g.29104719dup

Protein change:

V295fs

Links:

dbSNP: rs1187924885

NCBI 1000 Genomes Browser:

rs1187924885

Molecular consequence:

NM_001943.5:c.882dup - 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
SCV002151987	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17105751, 31386562, 20400443, 30790397, 28492532
SCV004183382	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 16, 2020)	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

SCV002151987

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 22, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004183382

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 16, 2020)

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

Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease.

Syrris P, Ward D, Asimaki A, Evans A, Sen-Chowdhry S, Hughes SE, McKenna WJ.

Eur Heart J. 2007 Mar;28(5):581-8. Epub 2006 Nov 14.

PubMed [citation]

PMID:: 17105751

Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmosomal Variants Are Rarely De Novo.

van Lint FHM, Murray B, Tichnell C, Zwart R, Amat N, Lekanne Deprez RH, Dittmann S, Stallmeyer B, Calkins H, van der Smagt JJ, van den Wijngaard A, Dooijes D, van der Zwaag PA, Schulze-Bahr E, Judge DP, Jongbloed JDH, van Tintelen JP, James CA.

Circ Genom Precis Med. 2019 Aug;12(8):e002467. doi: 10.1161/CIRCGEN.119.002467. Epub 2019 Aug 6.

PubMed [citation]

PMID:: 31386562

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002151987.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Val295Serfs*6) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 17105751, 31386562). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 20400443, 30790397). This variant is also known as c.882_883insA. ClinVar contains an entry for this variant (Variation ID: 691669). 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 Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV004183382.1

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

Description

ACMG classification criteria: PVS1, PM2

#	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: May 26, 2024

ClinVar

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