rs142841727

Variant names:

• chr18-31546145-T-C
• rs142841727
• NM_001943.5:c.2759T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-31546145-T-C
• chr18-31546145-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001943.5(DSG2):​c.2759T>C​(p.Val920Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V920I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSG2 NM_001943.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.145
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059398502).

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.2759T>C	p.Val920Ala	missense	Exon 15 of 15	NP_001934.2	Q14126
	DSG2-AS1	NR_045216.1		n.1346-239A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG2	ENST00000261590.13	TSL:1 MANE Select	c.2759T>C	p.Val920Ala	missense	Exon 15 of 15	ENSP00000261590.8	Q14126
	DSG2	ENST00000713817.1		c.2750T>C	p.Val917Ala	missense	Exon 16 of 16	ENSP00000519121.1	A0AAQ5BGZ7
	DSG2	ENST00000713819.1		c.2750T>C	p.Val917Ala	missense	Exon 17 of 17	ENSP00000519123.1	A0AAQ5BGZ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.71
DEOGEN2	Benign	0.094	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.14
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.055
Sift	Benign	0.50	T
Sift4G	Benign	0.67	T
Polyphen		0.012	B
Vest4		0.10
MutPred		0.28		Loss of sheet (P = 0.0457)
MVP		0.57
MPC		0.089
ClinPred		0.057	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.15
Mutation Taster		=98/2	polymorphism

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: rs142841727; hg19: chr18-29126108;