rs778978325
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP6
The NM_001127222.2(CACNA1A):c.2938C>T(p.Arg980Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,443,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R980G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001127222.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.2938C>T | p.Arg980Cys | missense_variant | 19/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.2938C>T | p.Arg980Cys | missense_variant | 19/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151814Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000165 AC: 1AN: 60460Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 35200
GnomAD4 exome AF: 0.00000232 AC: 3AN: 1291526Hom.: 0 Cov.: 32 AF XY: 0.00000314 AC XY: 2AN XY: 636232
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151814Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74140
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 30, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Episodic ataxia type 2;C4310716:Developmental and epileptic encephalopathy, 42 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at