Short QT syndrome

Gene: CACNA2D1

Amber List (moderate evidence)

CACNA2D1 (calcium voltage-gated channel auxiliary subunit alpha2delta 1)
EnsemblGeneIds (GRCh38): ENSG00000153956
EnsemblGeneIds (GRCh37): ENSG00000153956
OMIM: 114204, Gene2Phenotype
CACNA2D1 is in 4 panels

7 reviews

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: 18 Nov 2019, 2:45 p.m. | Last Modified: 18 Nov 2019, 2:45 p.m.
Panel Version: 1.23
Comment on mode of inheritance: MOI was corrected.
Created: 30 Sep 2019, 12:24 p.m. | Last Modified: 30 Sep 2019, 12:24 p.m.
Panel Version: 1.22

James Eden (Manchester)

I don't know

See table 1/figure 3 of Campuzano 2018, gene associated with Short QT syndrome. Only one patient with Short QT syndrome tested to date in Manchester.
Created: 25 Sep 2019, 1:15 p.m. | Last Modified: 25 Sep 2019, 1:31 p.m.
Panel Version: 1.20

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

Publications

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

I don't know

On CGGL Royal Brompton Panel currently, but no variants yet detected. Agree with limited evidence detailed in other reviews. more evidence needed
Created: 18 Sep 2019, 1:48 p.m. | Last Modified: 18 Sep 2019, 1:48 p.m.
Panel Version: 1.20

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

Rebecca Whittington (South West GLH)

I don't know

No associated phenotype on OMIM
Created: 25 Mar 2019, 4:30 p.m.
1 variant associated with SQT on HGMD. Also reported in controls 22840528. Some functional characterisation 29016797
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
Unknown

Ellen McDonagh (Genomics England Curator)

I don't know

Comment when marking as ready: Confirmed in the NHSE GMS Cardiology Specialist Group meeting call on 25th January 2019 that this gene should remain Amber.
Created: 4 Mar 2019, 9:15 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.

Sarah Leigh (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Taking into consideration the Expert review green, this gene is rated amber rather than red, awaiting further reports of Short QT syndrome 6.
Created: 19 Nov 2018, 12:54 p.m.
Not associated with Short QT phenotype in OMIM or in Gen2Phen, however, at least one variant has been reported in Short QT syndrome 6 (no others reported in the literature so far November 2018), together with supportive in vitro functional evidence (PMID: 21383000).
Created: 15 Nov 2018, 12:10 p.m.

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

Publications

Jules Hancox (University of Bristol)

Green List (high evidence)

Responsible for SQT6 variant of the SQTS.

Variable expressivity/penetrance

Functional evidence for loss of function
Sources: Literature
Created: 17 Oct 2018, 9:02 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
short qt; aborted sudden death; Brugada syndrome

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • South West GLH
  • London South GLH
  • North West GLH
  • UKGTN
  • Brugada syndrome (Version 1.7)
Phenotypes
  • short qt
  • Brugada syndrome
  • aborted sudden death
  • Short QT syndrome 6
Tags
watchlist
OMIM
114204
Clinvar variants
Variants in CACNA2D1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

30 Sep 2019, Gel status: 2

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: CACNA2D1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

4 Mar 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).

21 Feb 2019, Gel status: 2

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to CACNA2D1. Mode of inheritance for gene CACNA2D1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown

20 Feb 2019, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to CACNA2D1.

14 Feb 2019, Gel status: 2

Added New Source, Set publications

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to CACNA2D1. Publications for gene CACNA2D1 were changed from 21383000; 29759541; 29697308 to 30420954; 19862833; 16301704

20 Nov 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Jules Hancox: Responsible for SQT6 variant o

19 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).

19 Nov 2018, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag watchlist tag was added to gene: CACNA2D1.

19 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).

15 Nov 2018, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: cacna2d1 has been classified as Red List (Low Evidence).

15 Nov 2018, Gel status: 4

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: CACNA2D1 were set to PMID: 21383000; 29759541; 29697308

15 Nov 2018, Gel status: 3

Added New Source, Added New Source, Added New Source, Set mode of inheritance, Set Phenotypes, Status Update

Sarah Leigh (Genomics England Curator)

Source Brugada syndrome (Version 1.7) was added to CACNA2D1. Source Expert Review Green was added to CACNA2D1. Source UKGTN was added to CACNA2D1. Mode of inheritance for gene CACNA2D1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Short QT syndrome 6 for gene: CACNA2D1 Rating Changed from No List (delete) to Green List (high evidence)

17 Oct 2018, Gel status: 0

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

Jules Hancox (University of Bristol)

gene: CACNA2D1 was added gene: CACNA2D1 was added to Short QT syndrome. Sources: Literature Mode of inheritance for gene: CACNA2D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA2D1 were set to PMID: 21383000; 29759541; 29697308 Phenotypes for gene: CACNA2D1 were set to short qt; aborted sudden death; Brugada syndrome Review for gene: CACNA2D1 was set to GREEN