chr18-31549968-G-A

Variant names:

• chr18-31549968-G-A
• rs1667216
• ENST00000713780.1:c.*3225G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000713780.1(DSG2):​c.*3225G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,022 control chromosomes in the GnomAD database, including 21,864 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 0.51 (21864 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: DSG2 ENST00000713780.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG2-AS1	NR_045216.1	n.1345+70C>T		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000713780.1	c.*3225G>A		3_prime_UTR_variant	Exon 16 of 16			ENSP00000519082.1
DSG2-AS1	ENST00000583706.5	n.1383+70C>T		intron_variant	Intron 3 of 5	5
DSG2-AS1	ENST00000657343.1	n.696+70C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76771 AN: 151896 Hom.: 21815 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.506 AC: 76883 AN: 152014 Hom.: 21864 Cov.: 32 AF XY: 0.505 AC XY: 37515 AN XY: 74310

African (AFR) AF: 0.775 AC: 32117 AN: 41466

American (AMR) AF: 0.452 AC: 6899 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3671 AN: 5172

South Asian (SAS) AF: 0.342 AC: 1645 AN: 4812

European-Finnish (FIN) AF: 0.407 AC: 4295 AN: 10564

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25702 AN: 67948

Other (OTH) AF: 0.473 AC: 999 AN: 2114

Alfa AF: 0.400 Hom.: 6932

Bravo AF: 0.523

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		-0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1667216; hg19: chr18-29129931;