Variant rs55657337 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 NM_001943.5(DSG2):c.523+24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,533,416 control chromosomes in the GnomAD database, including 8,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2174 hom., cov: 31)

Exomes 𝑓: 0.10 ( 6270 hom. )

Consequence

DSG2
NM_001943.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.03

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:

DSG2 (HGNC:):

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=-0.83).

BP6

Variant 18-31521267-T-A is Benign according to our data. Variant chr18-31521267-T-A is described in ClinVar as [Benign]. Clinvar id is 188447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31521267-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 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.523+24T>A		intron_variant		ENST00000261590.13	NP_001934.2	Q14126
DSG2	XM_047437315.1 linkuse as main transcript	c.-12+24T>A		intron_variant			XP_047293271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13 linkuse as main transcript	c.523+24T>A		intron_variant		1	NM_001943.5	ENSP00000261590.8		Q14126

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22543

AN:

151174

Hom.:

2165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.0966

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.0389

Gnomad SAS

AF:

0.0787

Gnomad FIN

AF:

0.0582

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.0968

AC:

21021

AN:

217070

Hom.:

1127

AF XY:

0.0960

AC XY:

11416

AN XY:

118974

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.0566

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.0352

Gnomad SAS exome

AF:

0.0630

Gnomad FIN exome

AF:

0.0700

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.104

AC:

143978

AN:

1382134

Hom.:

6270

Cov.:

AF XY:

0.103

AC XY:

71051

AN XY:

689098

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.0612

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.0480

Gnomad4 SAS exome

AF:

0.0688

Gnomad4 FIN exome

AF:

0.0704

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.149

AC:

22584

AN:

151282

Hom.:

2174

Cov.:

AF XY:

0.144

AC XY:

10664

AN XY:

73926

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.0965

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.0390

Gnomad4 SAS

AF:

0.0794

Gnomad4 FIN

AF:

0.0582

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.131

Hom.:

278

Bravo

AF:

0.155

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	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.83

CADD

Benign

0.19

DANN

Benign

0.21

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