RASopathies

Gene: BRAF

Comment on mode of pathogenicity: Missense variants are likely to be most relevant. Some variants found within Cardio-facio-cutaneous syndrome patients have been linked to gain-of-function, though some missense variants do not show increased BRAF activity in the publications. Reported as activating mutation consequence in G2P. Comments from reviewer: Gain of function mutations in BRAF cause Noonan syndrome, Cardio-Facio-cutanenous syndrome and LEOPARD syndrome. This disorders share phenotypes with Legius syndrome. - Helen Savage (Congenica Ltd), Jan. 22, 2016, 10:59 a.m. Gain of functions mutations in BRAF are reported to cause up to 2% of cases of Noonan syndrome. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 11:48 a.m.

Created: 5 Feb 2016, 12:04 p.m.

Comment when marking as ready: This gene was promoted to green, as it has a strong evidence of being indicated in Noonan syndrome, LEOPARD syndrome and Cardio-facio-cutaneous syndrome, and as phenotypes are often difficult to distinguish, this gene should also be examined in patients recruited under the other rasopathy syndromes. This gene is part of the eligibility criteria for prior genetic testing of rasopathy patients.

Created: 4 Feb 2016, 3:33 p.m.

Green List (high evidence)

Gain of function mutations

Created: 27 Jan 2016, 4 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Noonan syndrome; LEOPARD syndrome; Cardio-facio-cutaneous 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