rs1057519429
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_001127222.2(CACNA1A):c.5015G>C(p.Arg1672Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. 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 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.5015G>C | p.Arg1672Pro | missense_variant | 32/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.5015G>C | p.Arg1672Pro | missense_variant | 32/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Spinocerebellar ataxia type 6;C1720416:Episodic ataxia type 2;C1832884:Migraine, familial hemiplegic, 1;C4479236:Developmental and epileptic encephalopathy, 52 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Wendy Chung Laboratory, Columbia University Medical Center | Mar 20, 2022 | - - |
Cerebellar ataxia;C0740279:Cerebellar atrophy;C3714756:Intellectual disability Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Undiagnosed Diseases Network, NIH | Dec 19, 2015 | Likely pathogenicity based on finding it once in our study de novo in an 8-year-old female with delayed motor milestones, delayed speech, progressive cerebellar atrophy, hypotonia, and problems with coordination. Our patient has been reported in PMCID:PMC5557584 (patient 1). - |
Cerebellar ataxia Pathogenic:1
Pathogenic, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | This variant was identified, de novo, in an individual with non-fluctuating ataxia. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at