3-50379822-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_Strong
The NM_006030.4(CACNA2D2):c.896G>A(p.Ser299Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006030.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.896G>A | p.Ser299Asn | missense_variant, splice_region_variant | 10/38 | ENST00000424201.7 | NP_006021.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.896G>A | p.Ser299Asn | missense_variant, splice_region_variant | 10/38 | 1 | NM_006030.4 | ENSP00000390329 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250820Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135650
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461588Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727072
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 | Labcorp Genetics (formerly Invitae), Labcorp | Apr 25, 2017 | In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs769848295, ExAC 0.002%) but has not been reported in the literature in individuals with a CACNA2D2-related disease. This sequence change replaces serine with asparagine at codon 299 of the CACNA2D2 protein (p.Ser299Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at