rs8093731

Positions:

• chr18-31508995-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001943.5(DSG2):​c.46-9244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,056 control chromosomes in the GnomAD database, including 1,347 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (1347 hom., cov: 32)
• Consequence: DSG2 NM_001943.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG2	NM_001943.5	c.46-9244C>T		intron_variant		ENST00000261590.13	NP_001934.2
DSG2	XM_047437315.1	c.-527-303C>T		intron_variant			XP_047293271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13	c.46-9244C>T		intron_variant		1	NM_001943.5	ENSP00000261590.8
DSG2	ENST00000683654.1	c.46-9244C>T		intron_variant				ENSP00000506971.1
DSG2	ENST00000682241.2	c.46-9244C>T		intron_variant				ENSP00000507600.2
DSG2	ENST00000585206.1	c.46-9244C>T		intron_variant		2		ENSP00000462503.1

Frequencies

GnomAD3 genomes AF: 0.0831 AC: 12628 AN: 151938 Hom.: 1352 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.00832

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0573

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0831 AC: 12643 AN: 152056 Hom.: 1347 Cov.: 32 AF XY: 0.0829 AC XY: 6161 AN XY: 74338

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.0311

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.00832

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0567

Alfa AF: 0.0281 Hom.: 369

Bravo AF: 0.0911

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.73

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: rs8093731; hg19: chr18-29088958;