rs749174176
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024422.6(DSC2):c.2318G>T(p.Gly773Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G773A) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
DSC2
NM_024422.6 missense
NM_024422.6 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 1.79
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.2318G>T | p.Gly773Val | missense_variant | 15/16 | ENST00000280904.11 | |
DSC2 | NM_004949.5 | c.2318G>T | p.Gly773Val | missense_variant | 15/17 | ||
DSC2 | NM_001406506.1 | c.1889G>T | p.Gly630Val | missense_variant | 15/16 | ||
DSC2 | NM_001406507.1 | c.1889G>T | p.Gly630Val | missense_variant | 15/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.2318G>T | p.Gly773Val | missense_variant | 15/16 | 1 | NM_024422.6 | P1 | |
DSC2 | ENST00000251081.8 | c.2318G>T | p.Gly773Val | missense_variant | 15/17 | 1 | |||
DSC2 | ENST00000648081.1 | c.1889G>T | p.Gly630Val | missense_variant | 16/17 | ||||
DSC2 | ENST00000682357.1 | c.1889G>T | p.Gly630Val | missense_variant | 15/16 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
EpiCase
AF:
EpiControl
AF:
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 submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 04, 2023 | Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the cytoplasmic domain of the DSC2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;.
Polyphen
P;D;.
Vest4
MutPred
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at