Menu
GeneBe

rs1131691712

Variant summary

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.

Frequency

Genomes: not found (cov: 31)

Consequence

CACNA1A
NM_001127222.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 0.323

Links

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 17 ACMG points.

PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 31.
PP5
?
Variant 19-13286952-G-GA is Pathogenic according to our data. Variant chr19-13286952-G-GA is described in ClinVar as [Pathogenic]. Clinvar id is 429987. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA1ANM_001127222.2 linkuse as main transcriptc.3103_3104insT p.Ser1035PhefsTer32 frameshift_variant 20/47 ENST00000360228.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA1AENST00000360228.11 linkuse as main transcriptc.3103_3104insT p.Ser1035PhefsTer32 frameshift_variant 20/471 NM_001127222.2 O00555-8

Frequencies

GnomAD3 genomes
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingAmbry GeneticsApr 28, 2016- -
not provided Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingGeneDxMay 04, 2017The 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1131691712; hg19: chr19-13397766;