RASopathies
Gene: BRAFComment 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.
Gain of function mutationsCreated: 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
Phenotypes for gene: BRAF were changed from LEOPARD Syndrome; Noonan Syndrome; Cardiofaciocutaneous Syndrome; LEOPARD syndrome 3; Cardio-facio-cutaneous syndrome to LEOPARD syndrome 3 613707; Cardiofaciocutaneous syndrome 115150; Noonan syndrome 7 613706
Publications for gene: BRAF were set to PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583
Phenotypes for gene BRAF were set to LEOPARD Syndrome;Noonan Syndrome;Cardiofaciocutaneous Syndrome;LEOPARD syndrome 3;Cardio-facio-cutaneous syndrome
Phenotypes for gene BRAF were set to LEOPARD Syndrome;Noonan Syndrome;Cardiofaciocutaneous Syndrome;LEOPARD syndrome 3;Cardio-facio-cutaneous syndrome
Phenotypes for BRAF were set to LEOPARD Syndrome; Noonan Syndrome; Cardiofaciocutaneous Syndrome; LEOPARD syndrome 3; Cardio-facio-cutaneous syndrome
Mode of pathogenicity for BRAF was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
This gene has been classified as Green List (High Evidence).
Phenotypes for BRAF were set to LEOPARD Syndrome; Noonan Syndrome; Cardiofaciocutaneous Syndrome; Costello Syndrome; Noonan-Like Syndrome with Loose Anagen Hair; LEOPARD syndrome 3; Cardio-facio-cutaneous syndrome
This gene has been classified as Green List (High Evidence).
Publications for BRAF were set to PMID: 19206169; 21396583
Mode of pathogenicity for BRAF was changed to Other - please provide details in the comments
Publications for BRAF were set to PMID: 19206169
Phenotypes for BRAF were set to LEOPARD Syndrome ; Noonan Syndrome; LEOPARD Syndrome; Cardiofaciocutaneous Syndrome; Costello Syndrome; Noonan-Like Syndrome with Loose Anagen Hair; LEOPARD syndrome 3; Cardio-facio-cutaneous syndrome
Mode of inheritance for BRAF was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene BRAF were set to LEOPARD Syndrome ; Noonan Syndrome; LEOPARD Syndrome; Cardiofaciocutaneous Syndrome; Costello Syndrome; Noonan-Like Syndrome with Loose Anagen Hair; LEOPARD syndrome 3
BRAF was added to RASopathiespanel. Sources: Eligibility statement prior genetic testing
BRAF was added to RASopathiespanel. Sources: Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN
BRAFAll sources for gene: BRAF were removed
Phenotypes for gene BRAF were set to Noonan Syndrome ;Noonan syndrome 7, ;Noonan Syndrome; LEOPARD Syndrome; Cardiofaciocutaneous Syndrome; Costello Syndrome; Noonan-Like Syndrome with Loose Anagen Hair; Noonan Spectrum Disorders;Cardiofaciocutaneous Syndrome ;Cardiofaciocutaneous syndrome;LEOPARD Syndrome ;LEOPARD syndrome 3 ;Noonan Spectrum Disorders;Noonan syndrome;Noonan syndrome plus other features;Cardio-facio-cutaneous syndrome;LEOPARD syndrome;Legius syndrome;Costello syndrome
BRAF was added to RASopathiespanel. Source: Illumina TruGenome Clinical Sequencing Services
BRAF was added to RASopathiespanel. Source: Illumina TruGenome Clinical Sequencing Services
BRAF was added to RASopathiespanel. Source: Illumina TruGenome Clinical Sequencing Services BRAF was added to RASopathiespanel. Source: Radboud University Medical Center, Nijmegen
BRAF was added to RASopathiespanel. Source: Radboud University Medical Center, Nijmegen
BRAF was added to RASopathiespanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Eligibility statement prior genetic testing
BRAF was created by ellenmcdonagh