Genes in panel
STRs in panel
Prev Next

Genetic epilepsy syndromes

Gene: CACNA1D

Green List (high evidence)

CACNA1D (calcium voltage-gated channel subunit alpha1 D)
EnsemblGeneIds (GRCh38): ENSG00000157388
EnsemblGeneIds (GRCh37): ENSG00000157388
OMIM: 114206, Gene2Phenotype
CACNA1D is in 8 panels

4 reviews

Helen Lord (Oxford Medical Genetics Laboratories)

Green List (high evidence)

Only 1 case reported with a hom variant who had epilepsy and deafness but wouldn't want to miss possible cases.
Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

de novo gain-of-function mutations. AD primary aldosteronism, seizures and neurological abnormalities and AR sinoatrial node dysfunction and deafness (no seizures associated with this). AD condition: Scholl et al, 2013 sequenced this gene in 100 unrelated individuals with unexplained early onset primary aldosteronism - 2 girls with de novo heterozygous GOF missense variants. Both patients had seizures. A few other cases reported on HGMD Pro.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Primary aldosteronism, seizures, and neurologic abnormalities,615474; Sinoatrial node dysfunction and deafness,614896

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Rebecca Foulger (Genomics England curator)

I don't know

Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review from Helen Lord.
Created: 7 Sep 2019, 10:42 a.m. | Last Modified: 7 Sep 2019, 10:42 a.m.
Panel Version: 1.274
Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on mode of inheritance: Primary aldosteronism, seizures, and neurologic abnormalities (MIM: 615474) has AD inheritance. Seizures are not generally reported for the biallelic disorder Sinoatrial node dysfunction and deafness (MIM:614896). However, PMID:30054272 report an Arabic individual from consanguineous parents with moderate hearing impairment, ID, DD and epilepsy and a homozygous missense variant in CACNA1D (Gln567His). Seizures began age 4 months. The individual also had a homozygous OTOG variant, but this was present in a heterozygous state in the gnomAD browser. Both parents were heterozygous for the OTOG and CACNA1D variants.
Created: 15 Jul 2019, 12:32 p.m. | Last Modified: 15 Jul 2019, 12:32 p.m.
Panel Version: 1.157

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Gain of function variants associated with Primary aldosteronism, seizures, and neurologic abnormalities 615474 in OMIM and as a probable G2P gene. At least 3 de novo variants reported in 3 unrelated cases. Global developmental delay and intellectual disability is associated with this phenotype.
Created: 19 Dec 2017, 1:45 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Primary aldosteronism, seizures, and neurologic abnormalities 615474 AD; Sinoatrial node dysfunction and deafness 614896 AR

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Wessex and West Midlands GLH
  • NHS GMS
  • Literature
  • Literature
Phenotypes
  • Primary aldosteronism, seizures, and neurologic abnormalities 615474 AD
  • Sinoatrial node dysfunction and deafness 614896 AR
OMIM
114206
Clinvar variants
Variants in CACNA1D
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

7 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: cacna1d has been classified as Green List (High Evidence).

7 Sep 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: CACNA1D was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to CACNA1D.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to CACNA1D.

15 Jul 2019, Gel status: 3

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for gene: CACNA1D was changed from None to Other

15 Jul 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: CACNA1D were set to 28472301; 23913001; 30698561

15 Jul 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: CACNA1D was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

15 Jul 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: CACNA1D were set to 28472301; 23913001

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Sarah Leigh: Gain of function variants asso

4 Apr 2018, Gel status: 4

Added New Source

Sarah Leigh (Genomics England Curator)

CACNA1D was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Literature

4 Apr 2018, Gel status: 4

Created

Sarah Leigh (Genomics England Curator)

CACNA1D was created by Sarah Leigh