rs369917706
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_006030.4(CACNA2D2):c.2599A>C(p.Asn867His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. N867S) 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.2599A>C | p.Asn867His | missense_variant | 30/38 | ENST00000424201.7 | |
LOC101928965 | NR_183064.1 | n.969+285T>G | intron_variant, non_coding_transcript_variant | ||||
LOC127898564 | NR_183066.1 | n.869+285T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.2599A>C | p.Asn867His | missense_variant | 30/38 | 1 | NM_006030.4 | P4 | |
ENST00000607121.5 | n.602+285T>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250500Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135664
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461628Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727094
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74462
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 867 of the CACNA2D2 protein (p.Asn867His). This variant is present in population databases (rs369917706, gnomAD 0.003%). 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: 411014). 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: "Benign"; Align-GVGD: "Class C15"). 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