chr19-13214276-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_001127222.2(CACNA1A):c.5897G>A(p.Arg1966Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000289 in 1,612,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1966L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001127222.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.5897G>A | p.Arg1966Gln | missense_variant | 40/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.5897G>A | p.Arg1966Gln | missense_variant | 40/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000401 AC: 61AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000594 AC: 147AN: 247600Hom.: 0 AF XY: 0.000609 AC XY: 82AN XY: 134586
GnomAD4 exome AF: 0.000277 AC: 405AN: 1459762Hom.: 0 Cov.: 31 AF XY: 0.000271 AC XY: 197AN XY: 726270
GnomAD4 genome ? AF: 0.000400 AC: 61AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74484
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 23, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 31, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is present in ExAC with a MaxMAF of 0.06%. It is predicted to be pathogenic by predictive tools. It is not present in ClinVar. It has been seen in 1 patient with congenital hyperinsulinism and 1 with epilepsy. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 17, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2019 | This variant is associated with the following publications: (PMID: 23869231, 21703448, 28488083) - |
Episodic ataxia type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | Aug 22, 2023 | - - |
Episodic ataxia type 2;C4310716:Developmental and epileptic encephalopathy, 42 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at