18-31521252-CTTTT-CTTTTT

Position:

• chr18-31521252-CTTTT-CTTTTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001943.5(DSG2):​c.523+24dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,334,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: DSG2 NM_001943.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.123

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 18-31521252-C-CT is Benign according to our data. Variant chr18-31521252-C-CT is described in ClinVar as [Benign]. Clinvar id is 1284866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00148 (200/134688) while in subpopulation AFR AF= 0.00223 (83/37264). AF 95% confidence interval is 0.00184. There are 0 homozygotes in gnomad4. There are 106 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 200 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00146 AC: 197 AN: 134690 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000610

Gnomad ASJ AF: 0.00126

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00121

Gnomad FIN AF: 0.00284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.000547

GnomAD4 exome AF: 0.0375 AC: 45003 AN: 1200166 Hom.: 0 Cov.: 0 AF XY: 0.0361 AC XY: 21657 AN XY: 600272

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0281

Gnomad4 EAS exome AF: 0.0237

Gnomad4 SAS exome AF: 0.0311

Gnomad4 FIN exome AF: 0.0342

Gnomad4 NFE exome AF: 0.0398

Gnomad4 OTH exome AF: 0.0352

GnomAD4 genome AF: 0.00148 AC: 200 AN: 134688 Hom.: 0 Cov.: 32 AF XY: 0.00163 AC XY: 106 AN XY: 65180

Gnomad4 AFR AF: 0.00223

Gnomad4 AMR AF: 0.000685

Gnomad4 ASJ AF: 0.00126

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.00284

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.000544

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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

Jun 19, 2023

- -

Arrhythmogenic right ventricular dysplasia 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs77324780; hg19: chr18-29101215;