rs371214569
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4BS1_Supporting
The NM_006030.4(CACNA2D2):c.1847G>A(p.Arg616Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000363 in 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 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 Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.1847G>A | p.Arg616Lys | missense_variant, splice_region_variant | 21/38 | ENST00000424201.7 | NP_006021.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.1847G>A | p.Arg616Lys | missense_variant, splice_region_variant | 21/38 | 1 | NM_006030.4 | ENSP00000390329.2 | ||
CACNA2D2 | ENST00000423994.6 | c.1847G>A | p.Arg616Lys | missense_variant, splice_region_variant | 21/39 | 5 | ENSP00000407393.2 | |||
CACNA2D2 | ENST00000266039.7 | c.1847G>A | p.Arg616Lys | missense_variant, splice_region_variant | 21/38 | 1 | ENSP00000266039.3 | |||
CACNA2D2 | ENST00000360963.7 | c.1640G>A | p.Arg547Lys | missense_variant, splice_region_variant | 21/38 | 1 | ENSP00000354228.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461084Hom.: 0 Cov.: 35 AF XY: 0.0000385 AC XY: 28AN XY: 726850
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 | Nov 23, 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. ClinVar contains an entry for this variant (Variation ID: 530497). This variant has not been reported in the literature in individuals affected with CACNA2D2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 616 of the CACNA2D2 protein (p.Arg616Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at