3-50365450-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006030.4(CACNA2D2):c.3004C>A(p.Arg1002Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,416 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 (★).
Frequency
Consequence
NM_006030.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.3004C>A | p.Arg1002Ser | missense_variant | Exon 35 of 38 | 1 | NM_006030.4 | ENSP00000390329.2 | ||
CACNA2D2 | ENST00000423994.6 | c.3028C>A | p.Arg1010Ser | missense_variant | Exon 36 of 39 | 5 | ENSP00000407393.2 | |||
CACNA2D2 | ENST00000266039.7 | c.3004C>A | p.Arg1002Ser | missense_variant | Exon 35 of 38 | 1 | ENSP00000266039.3 | |||
CACNA2D2 | ENST00000360963.7 | c.2797C>A | p.Arg933Ser | missense_variant | Exon 35 of 38 | 1 | ENSP00000354228.3 | |||
ENSG00000272104 | ENST00000606589.1 | c.128-847G>T | intron_variant | Intron 2 of 3 | 3 | ENSP00000476225.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249638Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135470
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461230Hom.: 0 Cov.: 36 AF XY: 0.00000825 AC XY: 6AN XY: 726944
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
In summary, this variant is a rare missense change with uncertain impact on protein function. 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs764066785, ExAC 0.009%) but has not been reported in the literature in individuals with a CACNA2D2-related disease. This sequence change replaces arginine with serine at codon 1002 of the CACNA2D2 protein (p.Arg1002Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at