rs772555143
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP2PP3BS1_Supporting
The NM_006030.4(CACNA2D2):c.2969C>T(p.Ala990Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000507 in 1,577,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to 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 Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.2969C>T | p.Ala990Val | missense_variant, splice_region_variant | 34/38 | ENST00000424201.7 | |
LOC101928965 | NR_183064.1 | n.273G>A | non_coding_transcript_exon_variant | 1/2 | |||
LOC127898564 | NR_183066.1 | n.835-662G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.2969C>T | p.Ala990Val | missense_variant, splice_region_variant | 34/38 | 1 | NM_006030.4 | P4 | |
ENST00000607121.5 | n.262G>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000524 AC: 1AN: 190762Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 101822
GnomAD4 exome AF: 7.01e-7 AC: 1AN: 1425534Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 705396
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74358
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2021 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 has not been reported in the literature in individuals affected with CACNA2D2-related conditions. This variant is present in population databases (rs772555143, ExAC 0.02%). This sequence change replaces alanine with valine at codon 990 of the CACNA2D2 protein (p.Ala990Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at