rs763772019
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006030.4(CACNA2D2):c.1672G>T(p.Val558Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,420 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V558M) has been classified as Uncertain significance.
Frequency
Consequence
NM_006030.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.1672G>T | p.Val558Leu | missense_variant | Exon 18 of 38 | 1 | NM_006030.4 | ENSP00000390329.2 | ||
CACNA2D2 | ENST00000423994.6 | c.1672G>T | p.Val558Leu | missense_variant | Exon 18 of 39 | 5 | ENSP00000407393.2 | |||
CACNA2D2 | ENST00000266039.7 | c.1672G>T | p.Val558Leu | missense_variant | Exon 18 of 38 | 1 | ENSP00000266039.3 | |||
CACNA2D2 | ENST00000360963.7 | c.1465G>T | p.Val489Leu | missense_variant | Exon 18 of 38 | 1 | ENSP00000354228.3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461210Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 726900
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CACNA2D2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with leucine at codon 558 of the CACNA2D2 protein (p.Val558Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at