18-31542538-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001943.5(DSG2):c.2020C>T(p.Pro674Ser) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001943.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSG2 | NM_001943.5 | c.2020C>T | p.Pro674Ser | missense_variant | Exon 14 of 15 | ENST00000261590.13 | NP_001934.2 | |
DSG2 | XM_047437315.1 | c.1486C>T | p.Pro496Ser | missense_variant | Exon 15 of 16 | XP_047293271.1 | ||
DSG2-AS1 | NR_045216.1 | n.1811-217G>A | intron_variant | Intron 5 of 5 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cardiomyopathy Uncertain:1
This missense variant replaces proline with serine at codon 674 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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. -
Arrhythmogenic right ventricular cardiomyopathy Uncertain:1
This missense variant replaces proline with serine at codon 674 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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. -
Arrhythmogenic right ventricular dysplasia 10 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, a(n) neutral and non-polar amino acid, with serine, a(n) neutral and polar amino acid, at codon 674 of the DSG2 protein (p.Pro674Ser). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.