Variant rs875989812 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_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

Scores

Splicing: ADA: 1.000

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.39

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3 linkuse as main transcript	c.121-1G>T		splice_acceptor_variant		ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 linkuse as main transcript	c.121-1G>T		splice_acceptor_variant		1	NM_201596.3	ENSP00000320025		Q08289-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

180

AN:

24742

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00493

Gnomad AMI

AF:

0.00538

Gnomad AMR

AF:

0.00943

Gnomad ASJ

AF:

0.00256

Gnomad EAS

AF:

0.00804

Gnomad SAS

AF:

0.00499

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.0263

Gnomad NFE

AF:

0.00783

Gnomad OTH

AF:

0.00602

GnomAD3 exomes

AF:

0.000619

AC:

AN:

71112

Hom.:

AF XY:

0.000517

AC XY:

AN XY:

38656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.000400

Gnomad EAS exome

AF:

0.000970

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000178

Gnomad NFE exome

AF:

0.000500

Gnomad OTH exome

AF:

0.000734

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0353

AC:

10107

AN:

286308

Hom.:

Cov.:

AF XY:

0.0320

AC XY:

4841

AN XY:

151194

show subpopulations

Gnomad4 AFR exome

AF:

0.0193

Gnomad4 AMR exome

AF:

0.00835

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.00660

Gnomad4 SAS exome

AF:

0.0229

Gnomad4 FIN exome

AF:

0.00275

Gnomad4 NFE exome

AF:

0.0458

Gnomad4 OTH exome

AF:

0.0245

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00735

AC:

182

AN:

24770

Hom.:

Cov.:

AF XY:

0.00774

AC XY:

AN XY:

11630

show subpopulations

Gnomad4 AFR

AF:

0.00507

Gnomad4 AMR

AF:

0.00944

Gnomad4 ASJ

AF:

0.00256

Gnomad4 EAS

AF:

0.00804

Gnomad4 SAS

AF:

0.00627

Gnomad4 FIN

AF:

0.0178

Gnomad4 NFE

AF:

0.00783

Gnomad4 OTH

AF:

0.00599

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Uncertain

0.95

MutationTaster

Benign

1.0

D;D;D;D;D

GERP RS

5.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.97

Position offset: 14

DS_AL_spliceai

1.0

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over