chr18-31069010-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The ENST00000280904.11(DSC2):​c.2392C>A​(p.Arg798=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R798R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

DSC2
ENST00000280904.11 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.64
Variant links:
Genes affected
DSC2 (HGNC:3036): (desmocollin 2) This gene encodes a member of the desmocollin protein subfamily. Desmocollins, along with desmogleins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmocollin family members on chromosome 18. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia-11, and reduced protein expression has been described in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 18-31069010-G-T is Benign according to our data. Variant chr18-31069010-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 192114.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.64 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DSC2NM_024422.6 linkuse as main transcriptc.2392C>A p.Arg798= synonymous_variant 15/16 ENST00000280904.11 NP_077740.1
DSC2NM_004949.5 linkuse as main transcriptc.2392C>A p.Arg798= synonymous_variant 15/17 NP_004940.1
DSC2NM_001406506.1 linkuse as main transcriptc.1963C>A p.Arg655= synonymous_variant 15/16 NP_001393435.1
DSC2NM_001406507.1 linkuse as main transcriptc.1963C>A p.Arg655= synonymous_variant 15/17 NP_001393436.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DSC2ENST00000280904.11 linkuse as main transcriptc.2392C>A p.Arg798= synonymous_variant 15/161 NM_024422.6 ENSP00000280904 P1Q02487-1
DSC2ENST00000251081.8 linkuse as main transcriptc.2392C>A p.Arg798= synonymous_variant 15/171 ENSP00000251081 Q02487-2
DSC2ENST00000648081.1 linkuse as main transcriptc.1963C>A p.Arg655= synonymous_variant 16/17 ENSP00000497441
DSC2ENST00000682357.1 linkuse as main transcriptc.1963C>A p.Arg655= synonymous_variant 15/16 ENSP00000507826

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterresearchBiesecker Lab/Clinical Genomics Section, National Institutes of HealthJun 24, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
2.3
DANN
Benign
0.55
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201548399; hg19: chr18-28648976; API