chr3-50364674-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_006030.4(CACNA2D2):āc.3424C>Gā(p.Arg1142Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1142C) has been classified as Uncertain significance.
Frequency
Consequence
NM_006030.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.3424C>G | p.Arg1142Gly | missense_variant | 38/38 | ENST00000424201.7 | |
LOC127898564 | NR_183066.1 | n.835-1623G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.3424C>G | p.Arg1142Gly | missense_variant | 38/38 | 1 | NM_006030.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 7.26e-7 AC: 1AN: 1377096Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1AN XY: 677330
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 13, 2022 | This variant has not been reported in the literature in individuals affected with CACNA2D2-related conditions. 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 is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1142 of the CACNA2D2 protein (p.Arg1142Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at