rs121908220
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_001127222.2(CACNA1A):c.4996C>T(p.Arg1666Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1666Q) 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 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.4996C>T | p.Arg1666Trp | missense_variant | 32/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.4996C>T | p.Arg1666Trp | missense_variant | 32/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461652Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727100
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Migraine, familial hemiplegic, 1 Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Jun 13, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Center of Genomic medicine, Geneva, University Hospital of Geneva | Apr 25, 2016 | Pathogenic variants in CACNA1A have been reported to cause familial hemiplegic migraine. Here we report a case of a female patient with hemiplegic migraine caused by a pathogenic variant in CACNA1A. - |
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 12, 2019 | Not found in the total gnomAD dataset, and the data is high quality (0/278210 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Statistically associated with disease, but in a single family (p < 0.05). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at