rs1791235

Variant names:

• chr18-31546707-T-C
• rs1791235
• NM_001943.5:c.3321T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-31546707-T-C
• chr18-31546707-T-A
• chr18-31546707-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001943.5(DSG2):​c.3321T>C​(p.Val1107Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,426 control chromosomes in the GnomAD database, including 136,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18918 hom., cov: 32)
  • Exomes 𝑓: 0.39 (117558 hom.)
• Consequence: DSG2 NM_001943.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: 0.618
• Publications: 21 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 18-31546707-T-C is Benign according to our data. Variant chr18-31546707-T-C is described in ClinVar as Benign. ClinVar VariationId is 44315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.618 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 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.3321T>C	p.Val1107Val	synonymous	Exon 15 of 15	NP_001934.2	Q14126
	DSG2-AS1	NR_045216.1		n.1346-801A>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.3321T>C	p.Val1107Val	synonymous	Exon 15 of 15	ENSP00000261590.8	Q14126
	DSG2	ENST00000713817.1		c.3312T>C	p.Val1104Val	synonymous	Exon 16 of 16	ENSP00000519121.1	A0AAQ5BGZ7
	DSG2	ENST00000713819.1		c.3312T>C	p.Val1104Val	synonymous	Exon 17 of 17	ENSP00000519123.1	A0AAQ5BGZ7

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72634 AN: 151890 Hom.: 18874 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.422 AC: 105152 AN: 249070 AF XY: 0.410

Gnomad AFR exome AF: 0.696

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.706

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.393 AC: 573623 AN: 1461416 Hom.: 117558 Cov.: 47 AF XY: 0.388 AC XY: 282438 AN XY: 727036

African (AFR) AF: 0.691 AC: 23114 AN: 33466

American (AMR) AF: 0.443 AC: 19824 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 8343 AN: 26134

East Asian (EAS) AF: 0.714 AC: 28358 AN: 39698

South Asian (SAS) AF: 0.325 AC: 28009 AN: 86248

European-Finnish (FIN) AF: 0.407 AC: 21740 AN: 53404

Middle Eastern (MID) AF: 0.357 AC: 2059 AN: 5766

European-Non Finnish (NFE) AF: 0.376 AC: 417452 AN: 1111586

Other (OTH) AF: 0.409 AC: 24724 AN: 60390

GnomAD4 genome AF: 0.479 AC: 72737 AN: 152010 Hom.: 18918 Cov.: 32 AF XY: 0.479 AC XY: 35574 AN XY: 74326

African (AFR) AF: 0.680 AC: 28182 AN: 41436

American (AMR) AF: 0.439 AC: 6712 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3466

East Asian (EAS) AF: 0.713 AC: 3678 AN: 5162

South Asian (SAS) AF: 0.340 AC: 1635 AN: 4804

European-Finnish (FIN) AF: 0.406 AC: 4298 AN: 10586

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25729 AN: 67974

Other (OTH) AF: 0.451 AC: 951 AN: 2110

Alfa AF: 0.410 Hom.: 66365

Bravo AF: 0.492

Asia WGS AF: 0.570 AC: 1983 AN: 3478

EpiCase AF: 0.371

EpiControl AF: 0.365

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	2	Arrhythmogenic right ventricular dysplasia 10 (2)
-	-	2	Cardiomyopathy (2)
-	-	2	not provided (2)
-	-	1	Arrhythmogenic right ventricular cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.3
DANN	Benign	0.85
PhyloP100		0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs1791235; hg19: chr18-29126670; COSMIC: COSV55197712; COSMIC: COSV55197712;