chr18-31498250-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001943.5(DSG2):​c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000904 in 1,105,720 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

DSG2
NM_001943.5 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.999
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DSG2NM_001943.5 linkuse as main transcriptc.-2C>T 5_prime_UTR_variant 1/15 ENST00000261590.13 NP_001934.2 Q14126
DSG2XM_047437315.1 linkuse as main transcriptc.-574C>T 5_prime_UTR_variant 1/16 XP_047293271.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DSG2ENST00000261590 linkuse as main transcriptc.-2C>T 5_prime_UTR_variant 1/151 NM_001943.5 ENSP00000261590.8 Q14126
DSG2ENST00000683654 linkuse as main transcriptc.-2C>T 5_prime_UTR_variant 1/7 ENSP00000506971.1 A0A804HIA2
DSG2ENST00000682241 linkuse as main transcriptc.-2C>T 5_prime_UTR_variant 1/7 ENSP00000507600.2 A0A804HJQ3
DSG2ENST00000585206 linkuse as main transcriptc.-2C>T 5_prime_UTR_variant 1/62 ENSP00000462503.1 J3KSI6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.04e-7
AC:
1
AN:
1105720
Hom.:
0
Cov.:
30
AF XY:
0.00000190
AC XY:
1
AN XY:
525666
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthDec 21, 2020This variant changes 1 nucleotide in the 5' untranslated region of the DSG2 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
18
DANN
Benign
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-29078213; API