chr10-18534199-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_201596.3(CACNB2):āc.1178T>Gā(p.Ile393Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,100 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I393T) has been classified as Uncertain significance.
Frequency
Consequence
NM_201596.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.1178T>G | p.Ile393Arg | missense_variant | 11/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.1016T>G | p.Ile339Arg | missense_variant | 10/13 | ENST00000377329.10 | |
LOC124902387 | XR_007062077.1 | n.598A>C | non_coding_transcript_exon_variant | 1/2 | |||
LOC124902386 | XR_007062076.1 | n.83+4995A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1178T>G | p.Ile393Arg | missense_variant | 11/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.1016T>G | p.Ile339Arg | missense_variant | 10/13 | 1 | NM_201590.3 | ||
ENST00000425669.1 | n.482+4995A>C | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251364Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461100Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726918
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Brugada syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 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. 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 not expected to disrupt CACNB2 protein function. ClinVar contains an entry for this variant (Variation ID: 1375258). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 339 of the CACNB2 protein (p.Ile339Arg). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2021 | The p.I339R variant (also known as c.1016T>G), located in coding exon 10 of the CACNB2 gene, results from a T to G substitution at nucleotide position 1016. The isoleucine at codon 339 is replaced by arginine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at