Variant 18-31521252-CTTTT-CTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001943.5(DSG2):c.523+24delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00716 in 134,440 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 3 hom., cov: 32)

Exomes 𝑓: 0.33 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DSG2
NM_001943.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.123

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 18-31521252-CT-C is Benign according to our data. Variant chr18-31521252-CT-C is described in ClinVar as [Benign]. Clinvar id is 188448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31521252-CT-C is described in Lovd as [Benign]. Variant chr18-31521252-CT-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00716 (963/134440) while in subpopulation EAS AF= 0.0156 (72/4610). AF 95% confidence interval is 0.0127. There are 3 homozygotes in gnomad4. There are 496 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 963 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG2	NM_001943.5 link	c.523+24delT		intron_variant		ENST00000261590.13	NP_001934.2	Q14126
DSG2	XM_047437315.1 link	c.-12+24delT		intron_variant			XP_047293271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13 link	c.523+24delT		intron_variant		1	NM_001943.5	ENSP00000261590.8		Q14126

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

961

AN:

134442

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00535

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0173

Gnomad MID

AF:

0.00690

Gnomad NFE

AF:

0.00339

Gnomad OTH

AF:

0.00384

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.335

AC:

324967

AN:

971340

Hom.:

Cov.:

AF XY:

0.340

AC XY:

163915

AN XY:

482352

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.381

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.368

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.00716

AC:

963

AN:

134440

Hom.:

Cov.:

AF XY:

0.00763

AC XY:

496

AN XY:

65022

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.00550

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.0156

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.0173

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.00327

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Feb 28, 2019

- -

Arrhythmogenic right ventricular dysplasia 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 27, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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