Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2_SupportingPP2PP3_Moderate
The NM_001127222(CACNA1A):c.5891A>G(p.Tyr1964Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Verdict is Uncertain_significance. Variant got 4 ACMG points.
GnomAD3 genomesCov.: 32
Submissions by phenotype
Inborn genetic diseases
|Uncertain significance, criteria provided, single submitter||clinical testing||Ambry Genetics||Feb 08, 2022||The c.5894A>G (p.Y1965C) alteration is located in coding exon 40 of the CACNA1A gene. This alteration results from an A to G substitution at nucleotide position 5894, causing the tyrosine (Y) at amino acid position 1965 to be replaced by a cysteine (C). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -|
|Uncertain significance, criteria provided, single submitter||clinical testing||GeneDx||Jun 27, 2023||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 -|
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