rs62095194

chr18-31524915-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.468

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]

ACMG classification

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	UniProt
DSG2	NM_001943.5	c.1014+27G>A		intron_variant		ENST00000261590.13
DSG2	XM_047437315.1	c.480+27G>A		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34818 AN: 152018 Hom.: 4340 Cov.: 33

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

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.: 31 AF XY: 0.263 AC XY: 190883 AN XY: 725050

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.: 33 AF XY: 0.233 AC XY: 17357 AN XY: 74360

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Other links and lift over

dbSNP: rs62095194; hg19: chr18-29104878; COSMIC: COSV55204347; COSMIC: COSV55204347;