rs267605294
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM1PP2BP4_ModerateBP6
The NM_001127222.2(CACNA1A):c.5336G>A(p.Arg1779Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R1779R) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.5336G>A | p.Arg1779Gln | missense_variant | 35/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.5336G>A | p.Arg1779Gln | missense_variant | 35/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152166Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249216Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135196
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461556Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727052
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152166Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2017 | The p.R1780Q variant (also known as c.5339G>A), located in coding exon 35 of the CACNA1A gene, results from a G to A substitution at nucleotide position 5339. The arginine at codon 1780 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 08, 2020 | - - |
Episodic ataxia type 2;C4310716:Developmental and epileptic encephalopathy, 42 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at