dbSNP rs1667216: DSG2:c.*3225G>A (chr18-31549968-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.626

Publications

2 publications found

Variant links:

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 links:

DSG2-AS1 (HGNC:51311): (DSG2 antisense RNA 1)

DSG2-AS1 links:

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new If you want to explore the variant's impact on the transcript ENST00000713780.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000713780.1. 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-AS1	NR_045216.1		n.1345+70C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSG2	ENST00000713780.1		c.*3225G>A	3_prime_UTR	Exon 16 of 16	ENSP00000519082.1	A0AAQ5BGT2
DSG2-AS1	ENST00000583706.5	TSL:5	n.1383+70C>T	intron	N/A
DSG2-AS1	ENST00000657343.1		n.696+70C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76771

AN:

151896

Hom.:

21815

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.506

AC:

76883

AN:

152014

Hom.:

21864

Cov.:

AF XY:

0.505

AC XY:

37515

AN XY:

74310

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1690

3381

5071

6762

8452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

(source)

DANN

Benign

0.37

PhyloP100

-0.63

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over