rs371146201

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1

The NM_001943.5(DSG2):c.2305G>A(p.Glu769Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000407 in 1,399,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

DSG2
NM_001943.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:6B:2

Conservation

PhyloP100: 3.81

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23726985).

BP6

Variant 18-31542823-G-A is Benign according to our data. Variant chr18-31542823-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 163217.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000129 (18/139630) while in subpopulation AFR AF = 0.000425 (16/37628). AF 95% confidence interval is 0.000266. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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.2305G>A	p.Glu769Lys	missense	Exon 14 of 15	NP_001934.2	Q14126
	DSG2-AS1	NR_045216.1		n.1810+279C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DSG2	ENST00000261590.13	TSL:1 MANE Select	c.2305G>A	p.Glu769Lys	missense	Exon 14 of 15	ENSP00000261590.8	Q14126
DSG2	ENST00000713817.1		c.2296G>A	p.Glu766Lys	missense	Exon 15 of 16	ENSP00000519121.1	A0AAQ5BGZ7
DSG2	ENST00000713819.1		c.2296G>A	p.Glu766Lys	missense	Exon 16 of 17	ENSP00000519123.1	A0AAQ5BGZ7

Frequencies

GnomAD3 genomes

AF:

0.000129

AC:

AN:

139630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000805

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000466

AC:

AN:

214594

AF XY:

0.0000343

show subpopulations

Gnomad AFR exome

AF:

0.000334

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1260008

Hom.:

Cov.:

AF XY:

0.0000242

AC XY:

AN XY:

620430

show subpopulations

African (AFR)

AF:

0.000714

AC:

AN:

26620

American (AMR)

AF:

0.000195

AC:

AN:

30786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17776

East Asian (EAS)

AF:

0.00

AC:

AN:

24790

South Asian (SAS)

AF:

0.0000128

AC:

AN:

78012

European-Finnish (FIN)

AF:

0.0000253

AC:

AN:

39578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4716

European-Non Finnish (NFE)

AF:

0.00000202

AC:

AN:

989926

Other (OTH)

AF:

0.000209

AC:

AN:

47804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000129

AC:

AN:

139630

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

66732

show subpopulations

African (AFR)

AF:

0.000425

AC:

AN:

37628

American (AMR)

AF:

0.0000805

AC:

AN:

12424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

4458

South Asian (SAS)

AF:

0.00

AC:

AN:

4284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66074

Other (OTH)

AF:

0.00

AC:

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000173

Hom.:

ESP6500AA

AF:

0.000751

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000496

AC:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Arrhythmogenic right ventricular cardiomyopathy (1)

Arrhythmogenic right ventricular dysplasia 10 (1)

Arrhythmogenic right ventricular dysplasia 10;C2752072:Dilated cardiomyopathy 1BB (1)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

M_CAP

Benign

0.056

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.7

PhyloP100

3.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

REVEL

Benign

0.23

Sift

Benign

0.20

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.25

MVP

0.84

MPC

0.43

ClinPred

0.53

GERP RS

6.0

Varity_R

0.092

gMVP

0.73

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over