RASopathies

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 22 panels

2 reviews

Ellen McDonagh (Genomics England Curator)

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.

Helen Savage (Congenica Ltd)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • LEOPARD syndrome 3 613707
  • Cardiofaciocutaneous syndrome 115150
  • Noonan syndrome 7 613706
OMIM
164757
Clinvar variants
Variants in BRAF
Penetrance
Complete
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
Panels with this gene

History Filter Activity

13 Jun 2019, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

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

13 Jun 2019, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: BRAF were set to PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583

8 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for gene BRAF were set to LEOPARD Syndrome;Noonan Syndrome;Cardiofaciocutaneous Syndrome;LEOPARD syndrome 3;Cardio-facio-cutaneous syndrome

8 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for gene BRAF were set to LEOPARD Syndrome;Noonan Syndrome;Cardiofaciocutaneous Syndrome;LEOPARD syndrome 3;Cardio-facio-cutaneous syndrome

5 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for BRAF were set to LEOPARD Syndrome; Noonan Syndrome; Cardiofaciocutaneous Syndrome; LEOPARD syndrome 3; Cardio-facio-cutaneous syndrome

4 Feb 2016, Gel status: 4

Set mode of pathogenicity

Ellen McDonagh (Genomics England Curator)

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

4 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

4 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

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

4 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

4 Feb 2016, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for BRAF were set to PMID: 19206169; 21396583

4 Feb 2016, Gel status: 4

Set mode of pathogenicity

Ellen McDonagh (Genomics England Curator)

Mode of pathogenicity for BRAF was changed to Other - please provide details in the comments

4 Feb 2016, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for BRAF were set to PMID: 19206169

4 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

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

4 Feb 2016, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for BRAF was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

2 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

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

2 Feb 2016, Gel status: 4

Upload gene information

Ellen McDonagh (Genomics England Curator)

BRAF was added to RASopathiespanel. Sources: Eligibility statement prior genetic testing

2 Feb 2016, Gel status: 4

Upload gene information

Ellen McDonagh (Genomics England Curator)

BRAF was added to RASopathiespanel. Sources: Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN

2 Feb 2016, Gel status: 7

clearsources

Ellen McDonagh (Genomics England Curator)

BRAFAll sources for gene: BRAF were removed

2 Feb 2016, Gel status: 7

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

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

18 Nov 2015, Gel status: 8

Added New Source

Ellen McDonagh (Genomics England Curator)

BRAF was added to RASopathiespanel. Source: Illumina TruGenome Clinical Sequencing Services

18 Nov 2015, Gel status: 6

Added New Source

Ellen McDonagh (Genomics England Curator)

BRAF was added to RASopathiespanel. Source: Illumina TruGenome Clinical Sequencing Services

18 Nov 2015, Gel status: 5

Added New Source

Ellen McDonagh (Genomics England Curator)

BRAF was added to RASopathiespanel. Source: Illumina TruGenome Clinical Sequencing Services BRAF was added to RASopathiespanel. Source: Radboud University Medical Center, Nijmegen

18 Nov 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

BRAF was added to RASopathiespanel. Source: Radboud University Medical Center, Nijmegen

18 Nov 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

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

18 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

BRAF was created by ellenmcdonagh