rs121917812
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_201596.3(CACNB2):c.1604C>T(p.Ser535Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,874 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CACNB2
NM_201596.3 missense
NM_201596.3 missense
Scores
3
4
12
Clinical Significance
Conservation
PhyloP100: 3.96
Genes affected
CACNB2 (HGNC:1402): (calcium voltage-gated channel auxiliary subunit beta 2) This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Feb 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3327601).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.1604C>T | p.Ser535Leu | missense_variant | 14/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.1442C>T | p.Ser481Leu | missense_variant | 13/13 | ENST00000377329.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1604C>T | p.Ser535Leu | missense_variant | 14/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.1442C>T | p.Ser481Leu | missense_variant | 13/13 | 1 | NM_201590.3 | ||
ENST00000425669.1 | n.377-46G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251360Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135846
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727240
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GnomAD4 genome ? Cov.: 30
GnomAD4 genome
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Cov.:
30
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brugada syndrome 4 Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 30, 2007 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2021 | The p.S481L variant (also known as c.1442C>T), located in coding exon 13 of the CACNB2 gene, results from a C to T substitution at nucleotide position 1442. The serine at codon 481 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.;.;T;T;.;.;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;.;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
M;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
A;A;A;A;A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;.;N;.;.;N;N;N;.;N;.
REVEL
Benign
Sift
Benign
T;T;T;.;.;T;.;.;T;T;T;.;T;.
Sift4G
Benign
T;T;T;.;.;T;T;T;T;T;T;T;T;.
Polyphen
B;P;D;.;.;B;.;.;.;B;B;.;.;.
Vest4
MutPred
Loss of phosphorylation at S535 (P = 0.0186);.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at