rs372494397

Variant names:

• chr18-31542551-G-A
• NM_001943.5:c.2033G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-31542551-G-A
• chr18-31542551-G-C
• chr18-31542551-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001943.5(DSG2):​c.2033G>A​(p.Gly678Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DSG2 NM_001943.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069768965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG2	NM_001943.5	c.2033G>A	p.Gly678Glu	missense_variant	Exon 14 of 15	ENST00000261590.13	NP_001934.2
DSG2	XM_047437315.1	c.1499G>A	p.Gly500Glu	missense_variant	Exon 15 of 16		XP_047293271.1
DSG2-AS1	NR_045216.1	n.1811-230C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13	c.2033G>A	p.Gly678Glu	missense_variant	Exon 14 of 15	1	NM_001943.5	ENSP00000261590.8
DSG2-AS1	ENST00000583706.5	n.1849-230C>T		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.33
DANN	Benign	0.58
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.18
Sift	Benign	0.075	T
Sift4G	Benign	0.12	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.32		Gain of solvent accessibility (P = 0.024);
MVP		0.41
MPC		0.11
ClinPred		0.058	T
GERP RS		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-29122514;