Dilated cardiomyopathy - adult and teen

Gene: RYR2

Green List (high evidence)

RYR2 (ryanodine receptor 2)
EnsemblGeneIds (GRCh38): ENSG00000198626
EnsemblGeneIds (GRCh37): ENSG00000198626
OMIM: 180902, Gene2Phenotype
RYR2 is in 13 panels

10 reviews

Kate Thomson (Oxford University Hospitals Foundation Trust)

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. This gene did not achieve a consensus Green rating; however, the group agreed that the existing evidence (published and in-house data) was sufficient to support inclusion in this panel.
Created: 9 Dec 2019, 1:19 p.m. | Last Modified: 9 Dec 2019, 1:19 p.m.
Panel Version: 0.61

James Eden (Manchester)

I don't know

RYR2 is not currently tested in Manchester for DCM. RYR2 (whole gene) is associated with ARVD and CPVT on OMIM. Limited association of RYR2 variants with DCM. The RYR2 exon 3 deletion was reported in one article in 2 families with CPVT combined with additional features of dilated cardiomyopathy (https://www.ncbi.nlm.nih.gov/pubmed/17875969). This deletion is more commonly associated with LVNC cardiomyopathy in the literature (https://www.ncbi.nlm.nih.gov/pubmed/24394973, https://www.ncbi.nlm.nih.gov/pubmed/26018045).
Created: 27 Sep 2019, 11:37 a.m. | Last Modified: 27 Sep 2019, 11:37 a.m.
Panel Version: 0.46

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

Phenotypes
Arrhythmogenic right ventricular dysplasia 2 600996; Ventricular tachycardia, catecholaminergic polymorphic, 1 604772

Publications

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Green List (high evidence)

On CGGL Royal Brompton DCM panel. Definitive CPVT gene, appropriate for DCM panel due to possible phenotypic overlap as some evidence for exon 3 deletion specifically associated with DCM.
Created: 19 Sep 2019, 10:14 p.m. | Last Modified: 8 Apr 2021, 11:42 p.m.
Panel Version: 1.13

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

Ivone Leong (Genomics England Curator)

I don't know

Submitted on behalf of the GMS Cardiology specialist group. Demoted from Green to Amber. The group has agreed that this gene should be Amber on this panel. Testing should involve dosage analysis only in this gene.
Created: 3 Dec 2019, 2:28 p.m. | Last Modified: 3 Dec 2019, 2:28 p.m.
Panel Version: 0.52
RYR2 is a green gene on the Arrhythmogenic cardiomyopathy (code: 134, version 1.25). It has been promoted from amber to green in this panel as the GMS Cardiology Specialist Group decided that all green genes that are present on the Arrhythmogenic cardiomyopathy panel should also be green on this panel because of the overlap in clinical presentation.
Created: 4 Sep 2019, 10:51 a.m. | Last Modified: 4 Sep 2019, 10:51 a.m.
Panel Version: 0.37

Rebecca Whittington (South West GLH)

Red List (low evidence)

Arrhythmogenic right ventricular dysplasia 2 (600996); Ventricular tachycardia, catecholaminergic polymorphic, 1 (604772)
Created: 25 Mar 2019, 4:30 p.m.
PubMED: 29567486 - core gene. Lots of entries on HGMDPro for CPVT as considered to be the main gene. Reported C5 RYR2 assoc with short QT. Multiple variants on HGMD however pathogenicity downgraded to VUS: Pubmed: 28404607. Insufficient evidence to include.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Ellen McDonagh (Genomics England Curator)

I don't know

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.

Anna de Burca (Genomics England Curator)

Green List (high evidence)

Discussed with NHS GMS cardiology specialist group 25.01.19. Only recurrent exon 3 deletion is reliably associated with ARVC.
Created: 4 Feb 2019, 7:27 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arrhythmogenic right ventricular cardiomyopathy

Publications

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Mode of pathogenicity
Other

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

Bill Newman (Manchester Centre for Genomic Medicine)

Green List (high evidence)

Caroline Wright (Genomics England Curator)

Comment when marking as ready: Lots of patient reported with ARVC/D and rare variants in RYR2
Created: 14 Feb 2016, 3:51 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert List
  • South West GLH
  • London South GLH
  • Wessex and West Midlands GLH
Phenotypes
  • Arrhythmogenic right ventricular dysplasia 2
  • Arrhythmogenic right ventricular dysplasia 2 (600996)
  • Ventricular tachycardia, catecholaminergic polymorphic, 1 (604772)
OMIM
180902
Clinvar variants
Variants in RYR2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Dec 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to RYR2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

3 Dec 2019, Gel status: 2

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Amber was added to RYR2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

12 Sep 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: RYR2 were changed from Arrhythmogenic right ventricular dysplasia 2 to Arrhythmogenic right ventricular dysplasia 2; Arrhythmogenic right ventricular dysplasia 2 (600996); Ventricular tachycardia, catecholaminergic polymorphic, 1 (604772)

12 Sep 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: RYR2 were set to 20301310

4 Sep 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ivone Leong (Genomics England Curator)

gene: RYR2 was added gene: RYR2 was added to Dilated cardiomyopathy - adult and teen. Sources: Expert Review Green,Expert List Mode of inheritance for gene: RYR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RYR2 were set to 20301310 Phenotypes for gene: RYR2 were set to Arrhythmogenic right ventricular dysplasia 2