Pituitary hormone deficiency
Gene: BRAF

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

2 reviews

Catherine Snow (Genomics England)

Green List (high evidence)

The rating of this gene has been updated to GREEN and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Created: 31 Jan 2023, 3:01 p.m. | Last Modified: 31 Jan 2023, 3:01 p.m.

Panel Version: 2.106

Created: 31 Jan 2023, 3:01 p.m.
Last Modified: 31 Jan 2023, 3:01 p.m.
Panel version: 2.106

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting from red to amber, but with a green recommendation following GMS review. 5 cases reported with functional data implicating pituitary hormone deficiencies.
Created: 16 Sep 2022, 4:37 p.m. | Last Modified: 16 Sep 2022, 4:37 p.m.

Panel Version: 2.31

Comment on mode of pathogenicity: All missense, activating variants
Created: 16 Sep 2022, 4:36 p.m. | Last Modified: 16 Sep 2022, 4:36 p.m.

Panel Version: 2.28

PMID: 33795686 - Gualtieri et al 2021 - report 5 unrelated patients with 4 different missense variants in BRAF. WES did not find any other likely causative variants. They all had Cardio-Facio-Cutaneous (CFC) syndrome and were identified to have features of Septo-Optic Dysplasia (SOD). Functional studies using HEK293T cells showed that the BRAF genetic variants are pathogenic and result in activation of the ERK/MAPK pathway. Mice expressing one of the variants found BRAF p.Q257R showed abnormalities in terminal differentiation of hormone-producing cells.
Created: 16 Sep 2022, 4:36 p.m. | Last Modified: 16 Sep 2022, 4:36 p.m.

Panel Version: 2.26

Review on behalf of Professor Mehul Dattani, UCL GOS Institute of Child Health/Great Ormond Street Hospital for Children. Gualtieri A, Kyprianou N, Gregory LC, Vignola ML, Nicholson JG, Tan R, Inoue SI, Scagliotti V, Casado P, Blackburn J, Abollo-Jimenez F, Marinelli E, Besser REJ, Hgler W, Karen Temple I, Davies JH, Gagunashvili A, Robinson ICAF, Camper SA, Davis SW, Cutillas PR, Gevers EF, Aoki Y,Dattani MT, Gaston-Massuet C.Nat Commun. 2021 Apr 1;12(1):2028. doi: 10.1038/s41467-021-21712-4.
Created: 14 Sep 2022, 4:44 p.m. | Last Modified: 14 Sep 2022, 4:44 p.m.

Panel Version: 2.15

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

Phenotypes
Cardiofaciocutaneous syndrome, OMIM:115150; cardiofaciocutaneous syndrome, MONDO:0015280

Publications

33795686

Created: 14 Sep 2022, 4:44 p.m.
Last Modified: 14 Sep 2022, 4:44 p.m.
Panel version: 2.26

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

NHS GMS
Expert Review Green
Expert review

Phenotypes

Cardiofaciocutaneous syndrome, OMIM:115150
cardiofaciocutaneous syndrome, MONDO:0015280

OMIM

164757

Clinvar variants

Variants in BRAF

Penetrance

None

Publications

33795686

Mode of Pathogenicity

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

Panels with this gene

History Filter Activity

1 Feb 2023, Gel status: 3

Removed Tag, Removed Tag

Catherine Snow (Genomics England)

Tag Q3_22_rating was removed from gene: BRAF. Tag Q3_22_NHS_review was removed from gene: BRAF.

31 Jan 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Catherine Snow (Genomics England)

Source Expert Review Green was added to BRAF. Source NHS GMS was added to BRAF. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

16 Sep 2022, Gel status: 2