NM_001943.5:c.1014+27G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001943.5(DSG2):​c.1014+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,609,016 control chromosomes in the GnomAD database, including 56,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4347 hom., cov: 33)
Exomes 𝑓: 0.26 ( 52582 hom. )

Consequence

DSG2
NM_001943.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.468

Publications

7 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 Gene-Disease associations (from GenCC):
  • arrhythmogenic right ventricular cardiomyopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • arrhythmogenic right ventricular dysplasia 10
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • dilated cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • dilated cardiomyopathy 1BB
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 18-31524915-G-A is Benign according to our data. Variant chr18-31524915-G-A is described in ClinVar as Benign. ClinVar VariationId is 258493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DSG2NM_001943.5 linkc.1014+27G>A intron_variant Intron 8 of 14 ENST00000261590.13 NP_001934.2 Q14126
DSG2XM_047437315.1 linkc.480+27G>A intron_variant Intron 9 of 15 XP_047293271.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DSG2ENST00000261590.13 linkc.1014+27G>A intron_variant Intron 8 of 14 1 NM_001943.5 ENSP00000261590.8 Q14126

Frequencies

GnomAD3 genomes
AF:
0.229
AC:
34818
AN:
152018
Hom.:
4340
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.129
Gnomad AMI
AF:
0.161
Gnomad AMR
AF:
0.259
Gnomad ASJ
AF:
0.176
Gnomad EAS
AF:
0.295
Gnomad SAS
AF:
0.222
Gnomad FIN
AF:
0.345
Gnomad MID
AF:
0.196
Gnomad NFE
AF:
0.264
Gnomad OTH
AF:
0.225
GnomAD2 exomes
AF:
0.258
AC:
64221
AN:
248536
AF XY:
0.256
show subpopulations
Gnomad AFR exome
AF:
0.126
Gnomad AMR exome
AF:
0.297
Gnomad ASJ exome
AF:
0.173
Gnomad EAS exome
AF:
0.296
Gnomad FIN exome
AF:
0.336
Gnomad NFE exome
AF:
0.260
Gnomad OTH exome
AF:
0.244
GnomAD4 exome
AF:
0.265
AC:
385964
AN:
1456880
Hom.:
52582
Cov.:
31
AF XY:
0.263
AC XY:
190883
AN XY:
725050
show subpopulations
African (AFR)
AF:
0.126
AC:
4213
AN:
33350
American (AMR)
AF:
0.294
AC:
13144
AN:
44674
Ashkenazi Jewish (ASJ)
AF:
0.174
AC:
4536
AN:
26088
East Asian (EAS)
AF:
0.320
AC:
12685
AN:
39646
South Asian (SAS)
AF:
0.227
AC:
19507
AN:
86106
European-Finnish (FIN)
AF:
0.333
AC:
17789
AN:
53372
Middle Eastern (MID)
AF:
0.179
AC:
1030
AN:
5758
European-Non Finnish (NFE)
AF:
0.269
AC:
297596
AN:
1107640
Other (OTH)
AF:
0.257
AC:
15464
AN:
60246
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
13215
26430
39646
52861
66076
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
9954
19908
29862
39816
49770
<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:
0.229
AC:
34837
AN:
152136
Hom.:
4347
Cov.:
33
AF XY:
0.233
AC XY:
17357
AN XY:
74360
show subpopulations
African (AFR)
AF:
0.130
AC:
5379
AN:
41514
American (AMR)
AF:
0.259
AC:
3958
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.176
AC:
612
AN:
3468
East Asian (EAS)
AF:
0.294
AC:
1523
AN:
5172
South Asian (SAS)
AF:
0.220
AC:
1060
AN:
4820
European-Finnish (FIN)
AF:
0.345
AC:
3641
AN:
10564
Middle Eastern (MID)
AF:
0.197
AC:
58
AN:
294
European-Non Finnish (NFE)
AF:
0.264
AC:
17971
AN:
67984
Other (OTH)
AF:
0.231
AC:
488
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1395
2791
4186
5582
6977
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
366
732
1098
1464
1830
<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:
0.231
Hom.:
829
Bravo
AF:
0.222
Asia WGS
AF:
0.289
AC:
1002
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.57
DANN
Benign
0.50
PhyloP100
-0.47
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

Publications

Other links and lift over

dbSNP: rs62095194; hg19: chr18-29104878; COSMIC: COSV55204347; COSMIC: COSV55204347; API