NM_001943.5(DSG2):c.912_941delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA (p.Asp304_Ser314delinsGluIleGlyTrpGlnIleLeuHisLeuLysTer) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 4, 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:: RCV003010011.2

Allele description [Variation Report for NM_001943.5(DSG2):c.912_941delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA (p.Asp304_Ser314delinsGluIleGlyTrpGlnIleLeuHisLeuLysTer)]

NM_001943.5(DSG2):c.912_941delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA (p.Asp304_Ser314delinsGluIleGlyTrpGlnIleLeuHisLeuLysTer)

Gene:

DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.912_941delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA (p.Asp304_Ser314delinsGluIleGlyTrpGlnIleLeuHisLeuLysTer)

HGVS:

NC_000018.10:g.31524786_31524815delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA
NG_007072.3:g.31545_31574delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA
NM_001943.5:c.912_941delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGAMANE SELECT
NP_001934.2:p.Asp304_Pro648delinsGluIleGlyTrpGlnIleLeuHisLeuLysTer
NP_001934.2:p.Asp304_Ser314delinsGluIleGlyTrpGlnIleLeuHisLeuLysTer
LRG_397t1:c.912_941del30insAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA
LRG_397:g.31545_31574delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA
LRG_397p1:p.Asp304_Pro648delinsGluIleGlyTrpGlnIleLeuHisLeuLysTer
NC_000018.9:g.29104749_29104778delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA
NM_001943.3:c.912_941del30insAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA

Molecular consequence:

NM_001943.5:c.912_941delinsAATTGGCTGGCAAATTTTACATTTGAAATGAAGGAGGTTATTTCCTTCATTTGAATTGGCTGGCAAATTTTACATTTGAAATGA - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003314668	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 4, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17105751, 31386562, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003314668

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 4, 2022)

germline

clinical testing

PubMed (3)
[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

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 (3)

Details of each submission

From Invitae, SCV003314668.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.Asp304_Ser314delins10*) 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).

#	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: Feb 20, 2024

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