rs875989812
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePP3_Moderate
The NM_201596.3(CACNB2):c.121-1G>T variant causes a splice acceptor change. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0073 ( 0 hom., cov: 0)
Exomes 𝑓: 0.035 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CACNB2
NM_201596.3 splice_acceptor
NM_201596.3 splice_acceptor
Scores
4
2
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 4.39
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 4 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.046394352 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PP3
?
BayesDel_addAF computational evidence supports a deleterious effect, 0.353
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.121-1G>T | splice_acceptor_variant | ENST00000324631.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.121-1G>T | splice_acceptor_variant | 1 | NM_201596.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 180AN: 24742Hom.: 0 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.000619 AC: 44AN: 71112Hom.: 0 AF XY: 0.000517 AC XY: 20AN XY: 38656
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0353 AC: 10107AN: 286308Hom.: 0 Cov.: 8 AF XY: 0.0320 AC XY: 4841AN XY: 151194
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00735 AC: 182AN: 24770Hom.: 0 Cov.: 0 AF XY: 0.00774 AC XY: 90AN XY: 11630
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | research | CSER _CC_NCGL, University of Washington | Mar 11, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
GERP RS
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 14
DS_AL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at