Brugada syndrome

Gene: CACNB2

Red List (low evidence)

CACNB2 (calcium voltage-gated channel auxiliary subunit beta 2)
EnsemblGeneIds (GRCh38): ENSG00000165995
EnsemblGeneIds (GRCh37): ENSG00000165995
OMIM: 600003, Gene2Phenotype
CACNB2 is in 4 panels

5 reviews

Rebecca Whittington (South West GLH)

I don't know

Brugada syndrome 4 (OMIM 611876)
Created: 25 Mar 2019, 4:30 p.m.
Not much evidence for this gene. Variant described in Cardeiro paper (19358333) is not convincing. Other variant from Antzelevitch paper (17224476) tracks in family with Brugada, ? Functional evidence and strong BI and no frequency.PMID:22840528
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
Unknown

Variants in this GENE are reported as part of current diagnostic practice

Ellen McDonagh (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Due to new expert reviews and disputed evidence for this gene-disease causation, this gene has been demoted from Green to Red.
Created: 27 Feb 2019, 9:57 a.m.
This gene was given a validity classification of Disputed by the ClinGen validity curation group and is reflected by providing a Red review here.The gene-disease summary was downloaded on 20th Feb 2019.For the full report and publications see the ClinGen Gene Validity Curation for each gene here: https://search.clinicalgenome.org/kb/gene-validity/10148
Created: 20 Feb 2019, 2:47 p.m.
This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.

Mode of inheritance
Disputed

Phenotypes
Brugada syndrome 1; MONDO_0011001

James Eden (Manchester)

Red List (low evidence)

Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 24 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: disputed association with Brugada syndrome (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Brugada syndrome 4 (611876)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Caroline Wright (Genomics England Curator)

Comment when marking as ready: In Manchester diagnostic panel
Multiple variants in unrelated individuals in OMIM
Created: 11 Feb 2016, 11:14 a.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

PMID 17224476 - Describe a new clinical entity consisting of ST-segment elevation V1-V3 and shorter than normal QTc. S481L segregation with ST elevation and shortened QTc with ajmaline challenge in 6 family members; only the proband and brother are described as symptomatic. PMID 19358333 - T11I variant identified in proband presenting with syncope St elevation negative T-wave QTc428. T11I is in a minor transcript that has an alternative exon 1. No details about family. PMID 22840528 - report 2 probands with variants in CACNB2B: V340I (found in 13 of 113696 European alleles on gnomAD) and E499D (found in 7 of 35436 Latino alleles on gnomAD). In conclusion - insufficient evidence for any one or combination of these variants to constitute high evidence.
Created: 25 Jan 2019, 1:15 p.m.

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
Unknown
Sources
  • Expert Review Red
  • South West GLH
  • London South GLH
  • North West GLH
  • Expert list
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Brugada syndrome 4
  • Brugada syndrome 4 (611876)
OMIM
600003
Clinvar variants
Variants in CACNB2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

27 Feb 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: cacnb2 has been classified as Red List (Low Evidence).

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to CACNB2. Mode of inheritance for gene CACNB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to CACNB2.

14 Feb 2019, Gel status: 3

Added New Source, Set Phenotypes, Set publications, Status Update

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to CACNB2. Added phenotypes Brugada syndrome 4 (611876) for gene: CACNB2 Publications for gene CACNB2 were changed from to 17224476; 27761167 Rating Changed from Green List (high evidence) to Green List (high evidence)

11 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene CACNB2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

CACNB2 was added to Brugada syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene CACNB2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

CACNB2 was added to Brugada syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene CACNB2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

CACNB2 was added to Brugada syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

CACNB2 was added to Brugada syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list