18-31544461-C-T

Position:

• chr18-31544461-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.2335-1260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,824 control chromosomes in the GnomAD database, including 5,316 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 0.26 (5316 hom., cov: 32)
• Consequence: DSG2 NM_001943.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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-AS1 (HGNC:51311): (DSG2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG2	NM_001943.5	c.2335-1260C>T		intron_variant		ENST00000261590.13	NP_001934.2
DSG2-AS1	NR_045216.1	n.1517-1066G>A		intron_variant, non_coding_transcript_variant
DSG2	XM_047437315.1	c.1801-1260C>T		intron_variant			XP_047293271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13	c.2335-1260C>T		intron_variant		1	NM_001943.5	ENSP00000261590	P1
DSG2-AS1	ENST00000583706.5	n.1555-1066G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39002 AN: 151706 Hom.: 5308 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.257 AC: 39025 AN: 151824 Hom.: 5316 Cov.: 32 AF XY: 0.263 AC XY: 19518 AN XY: 74206

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.246

Alfa AF: 0.243 Hom.: 3943

Bravo AF: 0.252

Asia WGS AF: 0.370 AC: 1284 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.56

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: rs12604517; hg19: chr18-29124424;