3-50376143-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BS1_Supporting
The NM_006030.4(CACNA2D2):c.1672G>A(p.Val558Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V558L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.1672G>A | p.Val558Met | missense_variant | 18/38 | ENST00000424201.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.1672G>A | p.Val558Met | missense_variant | 18/38 | 1 | NM_006030.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250836Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135784
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461210Hom.: 0 Cov.: 35 AF XY: 0.0000426 AC XY: 31AN XY: 726900
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74474
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 558 of the CACNA2D2 protein (p.Val558Met). This variant is present in population databases (rs763772019, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CACNA2D2-related conditions. ClinVar contains an entry for this variant (Variation ID: 583347). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at