rs779011503
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The ENST00000348261.11(CACNA1H):c.2704C>T(p.Arg902Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,593,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R902Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000348261.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.2704C>T | p.Arg902Trp | missense_variant | 12/35 | ENST00000348261.11 | NP_066921.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.2704C>T | p.Arg902Trp | missense_variant | 12/35 | 1 | NM_021098.3 | ENSP00000334198 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000271 AC: 39AN: 1441574Hom.: 0 Cov.: 31 AF XY: 0.0000280 AC XY: 20AN XY: 715016
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74384
ClinVar
Submissions by phenotype
Epilepsy, childhood absence, susceptibility to, 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 11, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 22, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects CACNA1H function (PMID: 16754686). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CACNA1H protein function. ClinVar contains an entry for this variant (Variation ID: 529571). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 16754686). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 902 of the CACNA1H protein (p.Arg902Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at