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Gene | BRAF |
Variant | G466A |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | BRAF G466A (also reported as G465A) lies within the protein kinase domain of the Braf protein (UniProt.org). The functional effect of G466A (also reported as G465A) is conflicting as it demonstrates both intermediate Braf kinase activity (PMID: 15035987) and low Braf kinase activity (PMID: 28783719), leads to Ras-dependent activation of downstream Erk in cell culture (PMID: 28783719), in one of two cell lines increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785), and results in decreased interaction with Mek in an in vitro assay (PMID: 38588399). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF G466X BRAF G466A |
Transcript | NM_004333.6 |
gDNA | chr7:g.140781611C>G |
cDNA | c.1397G>C |
Protein | p.G466A |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001378471.1 | chr7:g.140778000C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_001378473.1 | chr7:g.140777053C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
XM_047420766.1 | chr7:g.140778075C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140781611C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
NM_001378472.1 | chr7:g.140777053C>G | c.1397G>C | p.G466A | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF G466A | gastrointestinal system cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gastrointestinal system cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
BRAF G466A | lung adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in 1 and stable disease in 2 patients with lung adenocarcinoma harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
BRAF G466A | prostate cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with prostate cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
BRAF G466A | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G466A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
BRAF G466A | collecting duct carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in decreased FDG avidity in the metastases in a patient with metastatic Bellini duct carcinoma harboring BRAF G466A, whose disease remained stable for 11 months (PMID: 33669326). | 33669326 |
BRAF G466A | lung non-small cell carcinoma | predicted - sensitive | LTT462 + LXH 254 | Case Reports/Case Series | Actionable | In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF G466A achieving SD with over 25% tumor reduction (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... |