chr19-13235666-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_Strong
The NM_001127222.2(CACNA1A):c.5015G>A(p.Arg1672His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging 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. R1672C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001127222.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.5015G>A | p.Arg1672His | missense_variant | 32/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.5015G>A | p.Arg1672His | missense_variant | 32/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461676Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727114
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Developmental and epileptic encephalopathy, 42 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centogene AG - the Rare Disease Company | May 24, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at