Mosaic brain disorders - deep sequencing

Gene: BRAF

Green List (high evidence)

BRAF (B-Raf proto-oncogene, serine/threonine kinase)
EnsemblGeneIds (GRCh38): ENSG00000157764
EnsemblGeneIds (GRCh37): ENSG00000157764
OMIM: 164757, Gene2Phenotype
BRAF is in 24 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 31 May 2023, 3:20 p.m. | Last Modified: 31 May 2023, 3:20 p.m.
Panel Version: 0.123
Two individuals with focal cortical dysplasia (FCD) type III and IIIb, respectively, and a BRAF variant (c.T1799A:p.V600E) reported in PMID:36635388 - relatedness of cases is unclear but additional phenotypic information only available for one patient.

Another two cases also reported in PMID:36864519 with a somatic p.V600E BRAF variant. One patient had FCD type I while the other had FCD type IIIb (ganglioglioma).

A different BRAF variant (p.I61V) was also found in an individual with FCD type IIa (PMID:36226386).

BRAF has most frequently been implicated in low-grade epilepsy-associated tumours (PMID:32151273; 35687047; 36226386) rather than isolated FCD and it should be noted that epilepsy caused by malignant tumours is out of scope for this panel. FCD Type IIIb associated with tumours was reported in 2/5 cases described above, suggesting borderline suitability of BRAF for R429. However, there is evidence indicating that inclusion could be of benefit to some patients and therefore rating as Green to minimise risk of missed diagnoses.
Created: 31 May 2023, 3:19 p.m. | Last Modified: 31 May 2023, 3:19 p.m.
Panel Version: 0.122

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

Tom Cullup (Great Ormond Street Hospital)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
FCD type 1, FCDIII

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

History Filter Activity

11 Oct 2023, Gel status: 3

Added New Source

Sarah Leigh (Genomics England Curator)

Source NHS GMS was added to BRAF.

31 May 2023, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag somatic tag was added to gene: BRAF.

31 May 2023, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: BRAF were changed from 36635388; 36864519; 36226386 to Focal cortical dysplasia

31 May 2023, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: BRAF were set to

31 May 2023, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: BRAF were changed from to 36635388; 36864519; 36226386

31 May 2023, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

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

31 May 2023, Gel status: 1

Set mode of pathogenicity

Arina Puzriakova (Genomics England Curator)

Mode of pathogenicity for gene: BRAF was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

30 May 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

gene: BRAF was added gene: BRAF was added to Mosaic brain disorders - deep sequencing. Sources: Expert list Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted