rs3737378

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001943.5(DSG2):c.828+16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,609,640 control chromosomes in the GnomAD database, including 56,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4276 hom., cov: 33)

Exomes 𝑓: 0.26 ( 52089 hom. )

Consequence

DSG2
NM_001943.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.193

Publications

6 publications found

Variant links:

Genes affected

DSG2 (HGNC:3049): (desmoglein 2) This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. Mutations in this gene have been associated with arrhythmogenic right ventricular dysplasia, familial, 10. [provided by RefSeq, Jan 2016]

DSG2 Gene-Disease associations (from GenCC):

arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
arrhythmogenic right ventricular dysplasia 10
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy 1BB
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

DSG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-31524601-C-A is Benign according to our data. Variant chr18-31524601-C-A is described in ClinVar as [Benign]. Clinvar id is 258495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG2	NM_001943.5 link	c.828+16C>A		intron_variant	Intron 7 of 14	ENST00000261590.13	NP_001934.2	Q14126
DSG2	XM_047437315.1 link	c.294+16C>A		intron_variant	Intron 8 of 15		XP_047293271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13 link	c.828+16C>A		intron_variant	Intron 7 of 14	1	NM_001943.5	ENSP00000261590.8		Q14126

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34274

AN:

151992

Hom.:

4271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.222

GnomAD2 exomes

AF:

0.255

AC:

63014

AN:

246648

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.263

AC:

383752

AN:

1457530

Hom.:

52089

Cov.:

AF XY:

0.262

AC XY:

189805

AN XY:

725248

show subpopulations

African (AFR)

AF:

0.114

AC:

3807

AN:

33344

American (AMR)

AF:

0.292

AC:

13058

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4538

AN:

26108

East Asian (EAS)

AF:

0.319

AC:

12618

AN:

39544

South Asian (SAS)

AF:

0.225

AC:

19327

AN:

86016

European-Finnish (FIN)

AF:

0.333

AC:

17765

AN:

53334

Middle Eastern (MID)

AF:

0.177

AC:

1017

AN:

5762

European-Non Finnish (NFE)

AF:

0.267

AC:

296340

AN:

1108564

Other (OTH)

AF:

0.254

AC:

15282

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

13708

27416

41123

54831

68539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9916

19832

29748

39664

49580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.225

AC:

34283

AN:

152110

Hom.:

4276

Cov.:

AF XY:

0.230

AC XY:

17068

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.119

AC:

4943

AN:

41516

American (AMR)

AF:

0.255

AC:

3901

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

612

AN:

3470

East Asian (EAS)

AF:

0.293

AC:

1516

AN:

5170

South Asian (SAS)

AF:

0.220

AC:

1060

AN:

4826

European-Finnish (FIN)

AF:

0.345

AC:

3634

AN:

10542

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17931

AN:

67982

Other (OTH)

AF:

0.228

AC:

483

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1352

2704

4055

5407

6759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.229

Hom.:

817

Bravo

AF:

0.217

Asia WGS

AF:

0.287

AC:

995

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:1

Sep 23, 2022

Cohesion Phenomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Arrhythmogenic right ventricular dysplasia 10

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.99

(source)

DANN

Benign

0.32

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over