Mosaic brain disorders - deep sequencing

Gene: CCND2

The rating of this gene has been updated to Red and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 8:53 a.m. | Last Modified: 11 Oct 2023, 8:53 a.m.

Panel Version: 0.133

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

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, OMIM:615938

Publications

• PMID: 24705253

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

I don't know

Comment on list classification: Following further consultation with colleagues from the requesting specialist team (Thomas Cullup and Amy McTague) it has been agreed that the rating of this gene can be updated from Red to Amber to allow the providing GLH to analyse and report on it if they feel it is appropriate for their cases. This would facilitate further gathering of data which could potentially support future promotion to green.

Created: 16 Oct 2023, 11:28 a.m. | Last Modified: 16 Oct 2023, 11:28 a.m.

Panel Version: 0.136

Comment on list classification: Seizures are not a reported feature of the associated phenotype and mosaicism is not typical. Only a single case where a patient's mother was mosaic for the probands variants and had some mild features including a large head, hypertelorism, and borderline intelligence (PMID: 24705253). Overall the evidence is not sufficient for adding this gene as diagnostic-grade and therefore recommending a Red gene rating at this time.

Created: 21 Dec 2022, 2:35 p.m. | Last Modified: 21 Dec 2022, 2:35 p.m.

Panel Version: 0.17

Red List (low evidence)

The rating of this gene has been updated to Red and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 5:26 p.m. | Last Modified: 1 Feb 2023, 5:38 p.m.

Panel Version: 0.93

Review submitted on behalf of Dr Lara Menzies, Dr Wendy Jones, Dr Amy McTague. Mode of inheritance: not given. Publications: Mirzaa et al 2014 Nature Genetics. Mechanism: GOF (MTOR pathway). Penetrance: no information provided.

Created: 21 Dec 2022, 12:16 p.m. | Last Modified: 21 Dec 2022, 12:16 p.m.

Panel Version: 0.2

Phenotypes
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

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