NM_001943.5:c.1014+27G>A

Variant names:

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.1014+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,609,016 control chromosomes in the GnomAD database, including 56,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4347 hom., cov: 33)

Exomes 𝑓: 0.26 ( 52582 hom. )

Consequence

DSG2
NM_001943.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.468

Publications

7 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=-0.84).

BP6

Variant 18-31524915-G-A is Benign according to our data. Variant chr18-31524915-G-A is described in ClinVar as Benign. ClinVar VariationId is 258493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG2	NM_001943.5 link	c.1014+27G>A		intron_variant	Intron 8 of 14	ENST00000261590.13	NP_001934.2	Q14126
DSG2	XM_047437315.1 link	c.480+27G>A		intron_variant	Intron 9 of 15		XP_047293271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13 link	c.1014+27G>A		intron_variant	Intron 8 of 14	1	NM_001943.5	ENSP00000261590.8		Q14126

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34818

AN:

152018

Hom.:

4340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.258

AC:

64221

AN:

248536

AF XY:

0.256

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.260

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.265

AC:

385964

AN:

1456880

Hom.:

52582

Cov.:

AF XY:

0.263

AC XY:

190883

AN XY:

725050

show subpopulations

African (AFR)

AF:

0.126

AC:

4213

AN:

33350

American (AMR)

AF:

0.294

AC:

13144

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4536

AN:

26088

East Asian (EAS)

AF:

0.320

AC:

12685

AN:

39646

South Asian (SAS)

AF:

0.227

AC:

19507

AN:

86106

European-Finnish (FIN)

AF:

0.333

AC:

17789

AN:

53372

Middle Eastern (MID)

AF:

0.179

AC:

1030

AN:

5758

European-Non Finnish (NFE)

AF:

0.269

AC:

297596

AN:

1107640

Other (OTH)

AF:

0.257

AC:

15464

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

13215

26430

39646

52861

66076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9954

19908

29862

39816

49770

<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:

0.229

AC:

34837

AN:

152136

Hom.:

4347

Cov.:

AF XY:

0.233

AC XY:

17357

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.130

AC:

5379

AN:

41514

American (AMR)

AF:

0.259

AC:

3958

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

612

AN:

3468

East Asian (EAS)

AF:

0.294

AC:

1523

AN:

5172

South Asian (SAS)

AF:

0.220

AC:

1060

AN:

4820

European-Finnish (FIN)

AF:

0.345

AC:

3641

AN:

10564

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17971

AN:

67984

Other (OTH)

AF:

0.231

AC:

488

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1395

2791

4186

5582

6977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.231

Hom.:

829

Bravo

AF:

0.222

Asia WGS

AF:

0.289

AC:

1002

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.84

CADD

Benign

0.57

(source)

DANN

Benign

0.50

PhyloP100

-0.47

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