Dilated cardiomyopathy - adult and teen

Gene: ACTN2

Green List (high evidence)

ACTN2 (actinin alpha 2)
EnsemblGeneIds (GRCh38): ENSG00000077522
EnsemblGeneIds (GRCh37): ENSG00000077522
OMIM: 102573, Gene2Phenotype
ACTN2 is in 9 panels

8 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

Ivone Leong (Genomics England Curator)

I don't know

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.
Created: 3 Dec 2019, 2:28 p.m. | Last Modified: 3 Dec 2019, 2:28 p.m.
Panel Version: 0.52

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

I don't know

Rebecca Whittington (South West GLH)

Green List (high evidence)

OMIM#612158: Cardiomyopathy, dilated 1AA with or without LVNC and Cardiomyopathy, hypertrophic, 23, with or without LVNC
Created: 25 Mar 2019, 4:30 p.m.
11 variants on HGMD assoc with DCM - 5 classed as DM in a number of literature reviews. Note Walsh 2017 classes all variants found in their cohort as VUS. In reviews: Dalin 2017 International Journal of Cardiology 228 (2017) 742748, Hershberger 2013 Nat Rev Cardiol 10:531 and Pugh (2014) Genet Med 16, 601 - note no L pathogenic variants reported.
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

Comment on list classification: This gene appears on 3/4 gene lists submitted from GLHs, however has a Red review from one of these labs and therefore demoted to Amber for further discussion.
Created: 24 Mar 2019, 10:16 a.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.

James Eden (Manchester)

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 47 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: currently no stated association with DCM, moderate association with intrinsic cardiomyopathy (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

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

Phenotypes
Cardiomyopathy, dilated, 1AA, with or without LVNC (612158); Cardiomyopathy, hypertrophic, 23, with or without LVNC (612158)

Publications

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

Caroline Wright (Genomics England Curator)

Comment when marking as ready: On Manchester diagnostic panel
Created: 14 Feb 2016, 4:12 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • South West GLH
  • Illumina TruGenome Clinical Sequencing Services
  • London South GLH
  • North West GLH
  • Expert list
  • Emory Genetics Laboratory
  • South West GLH
  • London South GLH
  • North West GLH
Phenotypes
  • Cardiomyopathy, hypertrophic, 23, with or without LVNC (612158)
  • Cardiomyopathy, dilated, 1AA, with or without LVNC (612158)
  • Dilated Cardiomyopathy, Dominant
OMIM
102573
Clinvar variants
Variants in ACTN2
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 ACTN2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

24 Mar 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: actn2 has been classified as Amber List (Moderate Evidence).

8 Mar 2019, Gel status: 4

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

Ellen McDonagh (Genomics England Curator)

gene: ACTN2 was added gene: ACTN2 was added to Dilated cardiomyopathy - adult and teen. Sources: Emory Genetics Laboratory,Expert list,North West GLH,Expert Review Green,London South GLH,Illumina TruGenome Clinical Sequencing Services,South West GLH,UKGTN Mode of inheritance for gene: ACTN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ACTN2 were set to 25224718; 27532257; 26312134 Phenotypes for gene: ACTN2 were set to Cardiomyopathy, hypertrophic, 23, with or without LVNC (612158); Cardiomyopathy, dilated, 1AA, with or without LVNC (612158); Dilated Cardiomyopathy, Dominant