Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PVS1PM2_SupportingPP5_Very_Strong
The NM_001127222.2(CACNA1A):c.3103_3104insT(p.Ser1035PhefsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S1035S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Verdict is Pathogenic. Variant got 17 ACMG points.
GnomAD3 genomesCov.: 31
Submissions by phenotype
Inborn genetic diseases
|Pathogenic, criteria provided, single submitter||clinical testing||Ambry Genetics||Apr 28, 2016||- -|
|Pathogenic, criteria provided, single submitter||clinical testing||GeneDx||May 04, 2017||The c.3106dupT variant in the CACNA1A gene has not been reported previously as a pathogenicvariant nor as a benign variant, to our knowledge. The c.3106dupT variant causes a frameshift startingwith codon Serine 1036, changes this amino acid to a Phenylalanine residue, and creates a prematureStop codon at position 32 of the new reading frame, denoted p.Ser1036PhefsX32. This variant ispredicted to cause loss of normal protein function either through protein truncation or nonsensemediatedmRNA decay. The c.3106dupT variant is not observed in large population cohorts (Lek etal., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.3106dupTas a pathogenic variant. -|
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