18-31544461-C-T

Variant names:

• chr18-31544461-C-T
• rs12604517
• NM_001943.5:c.2335-1260C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001943.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG2	NM_001943.5	MANE Select	c.2335-1260C>T		intron	N/A	NP_001934.2	Q14126
	DSG2-AS1	NR_045216.1		n.1517-1066G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG2	ENST00000261590.13	TSL:1 MANE Select	c.2335-1260C>T		intron	N/A	ENSP00000261590.8	Q14126
	DSG2	ENST00000713817.1		c.2326-1260C>T		intron	N/A	ENSP00000519121.1	A0AAQ5BGZ7
	DSG2	ENST00000713819.1		c.2326-1260C>T		intron	N/A	ENSP00000519123.1	A0AAQ5BGZ7

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

African (AFR) AF: 0.197 AC: 8168 AN: 41380

American (AMR) AF: 0.264 AC: 4030 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3466

East Asian (EAS) AF: 0.504 AC: 2604 AN: 5162

South Asian (SAS) AF: 0.251 AC: 1206 AN: 4802

European-Finnish (FIN) AF: 0.347 AC: 3645 AN: 10504

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18031 AN: 67962

Other (OTH) AF: 0.246 AC: 518 AN: 2104

Alfa AF: 0.245 Hom.: 4625

Bravo AF: 0.252

Asia WGS AF: 0.370 AC: 1284 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12604517; hg19: chr18-29124424;