rs368699159
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_006030.4(CACNA2D2):āc.2297A>Cā(p.Lys766Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000685 in 1,459,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_006030.4 missense, splice_region
Scores
Clinical Significance
Conservation
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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.2297A>C | p.Lys766Thr | missense_variant, splice_region_variant | 26/38 | ENST00000424201.7 | |
LOC101928965 | NR_183064.1 | n.970-154T>G | intron_variant, non_coding_transcript_variant | ||||
LOC127898564 | NR_183066.1 | n.870-154T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.2297A>C | p.Lys766Thr | missense_variant, splice_region_variant | 26/38 | 1 | NM_006030.4 | P4 | |
ENST00000607121.5 | n.603-154T>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1459422Hom.: 0 Cov.: 34 AF XY: 0.00000827 AC XY: 6AN XY: 725540
GnomAD4 genome Cov.: 32
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 | Aug 12, 2021 | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CACNA2D2-related disease. This variant is present in population databases (rs368699159, ExAC 0.002%). This sequence change replaces lysine with threonine at codon 766 of the CACNA2D2 protein (p.Lys766Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. 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