rs1555627137
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001943.5(DSG2):c.1277C>T(p.Ala426Val) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A426T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001943.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSG2 | NM_001943.5 | c.1277C>T | p.Ala426Val | missense_variant | 9/15 | ENST00000261590.13 | |
DSG2 | XM_047437315.1 | c.743C>T | p.Ala248Val | missense_variant | 10/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSG2 | ENST00000261590.13 | c.1277C>T | p.Ala426Val | missense_variant | 9/15 | 1 | NM_001943.5 | P1 | |
DSG2 | ENST00000683614.2 | n.1108C>T | non_coding_transcript_exon_variant | 7/7 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 02, 2017 | This sequence change replaces alanine with valine at codon 426 of the DSG2 protein (p.Ala426Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DSG2-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function but to affect mRNA splicing. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at