Variant rs62095194 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000261590.13(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
ENST00000261590.13 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.468

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 258493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31524915-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
DSG2	NM_001943.5 linkuse as main transcript	c.1014+27G>A		intron_variant		ENST00000261590.13	NP_001934.2
DSG2	XM_047437315.1 linkuse as main transcript	c.480+27G>A		intron_variant			XP_047293271.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
DSG2	ENST00000261590.13 linkuse as main transcript	c.1014+27G>A	intron_variant		1	NM_001943.5	ENSP00000261590	P1
DSG2	ENST00000682087.2 linkuse as main transcript	n.872G>A	non_coding_transcript_exon_variant	6/6
DSG2	ENST00000683614.2 linkuse as main transcript	n.845+27G>A	intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.258

AC:

64221

AN:

248536

Hom.:

8797

AF XY:

0.256

AC XY:

34484

AN XY:

134890

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 SAS exome

AF:

0.229

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

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.320

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.229

AC:

34837

AN:

152136

Hom.:

4347

Cov.:

AF XY:

0.233

AC XY:

17357

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.234

Hom.:

820

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.57

DANN

Benign

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over