chr10-18150882-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate
The NM_201596.3(CACNB2):c.121-1G>T variant causes a splice acceptor, intron 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, intron
NM_201596.3 splice_acceptor, intron
Scores
4
2
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 4.39
Publications
1 publications found
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]
CACNB2 Gene-Disease associations (from GenCC):
- Brugada syndrome 4Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine
- Brugada syndrome 1Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- short QT syndromeInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.046898637 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00728 AC: 180AN: 24742Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
180
AN:
24742
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000619 AC: 44AN: 71112 AF XY: 0.000517 show subpopulations
GnomAD2 exomes
AF:
AC:
44
AN:
71112
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
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 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
10107
AN:
286308
Hom.:
Cov.:
8
AF XY:
AC XY:
4841
AN XY:
151194
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
148
AN:
7682
American (AMR)
AF:
AC:
95
AN:
11378
Ashkenazi Jewish (ASJ)
AF:
AC:
99
AN:
7986
East Asian (EAS)
AF:
AC:
111
AN:
16822
South Asian (SAS)
AF:
AC:
311
AN:
13600
European-Finnish (FIN)
AF:
AC:
51
AN:
18540
Middle Eastern (MID)
AF:
AC:
20
AN:
1090
European-Non Finnish (NFE)
AF:
AC:
8925
AN:
195070
Other (OTH)
AF:
AC:
347
AN:
14140
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.287
Heterozygous variant carriers
0
791
1582
2374
3165
3956
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
430
860
1290
1720
2150
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
182
AN:
24770
Hom.:
Cov.:
0
AF XY:
AC XY:
90
AN XY:
11630
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
31
AN:
6118
American (AMR)
AF:
AC:
23
AN:
2436
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
782
East Asian (EAS)
AF:
AC:
5
AN:
622
South Asian (SAS)
AF:
AC:
5
AN:
798
European-Finnish (FIN)
AF:
AC:
12
AN:
676
Middle Eastern (MID)
AF:
AC:
1
AN:
40
European-Non Finnish (NFE)
AF:
AC:
100
AN:
12778
Other (OTH)
AF:
AC:
2
AN:
334
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.339
Heterozygous variant carriers
0
9
18
26
35
44
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brugada syndrome Uncertain:1
Mar 11, 2015
CSER _CC_NCGL, University of Washington
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
PhyloP100
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
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
Publications
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