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Gene | DNMT3A |
Variant | G707fs |
Impact List | frameshift |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | DNMT3A G707fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 707 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). G707fs has not been characterized, however, due to the effects of other truncation mutations downstream of G707 (PMID: 28872462, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function. |
Associated Drug Resistance | |
Category Variants Paths |
DNMT3A mutant DNMT3A inact mut DNMT3A G707fs |
Transcript | NM_022552.5 |
gDNA | chr2:g.(25240694_25240695) |
cDNA | c.(2119_2118) |
Protein | p.G707fs |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_005264175.5 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
NM_175629.2 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
XM_005264175.6 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
XM_047443593.1 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
NM_022552.4 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
XM_011532664.2 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
NM_022552.5 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
XM_017003526.1 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
XM_011532664.3 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
NM_175629.2 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
XM_017003526.2 | chr2:g.(25240694_25240695) | c.(2119_2118) | p.G707fs | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
DNMT3A mutant | acute myeloid leukemia | not applicable | N/A | Clinical Study | Prognostic | In clinical analyses, mutations in DNMT3A were associated with poor prognosis and shorter overall survival in patients with acute myeloid leukemia (PMID: 22490330, PMID: 21881046, PMID: 21670448). | 22490330 21881046 21670448 |
DNMT3A mutant | acute myeloid leukemia | sensitive | Pinometostat | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Pinometostat (EPZ-5676) treatment of acute myeloid leukemia cell lines and xenografts resulted in apoptosis, cell-cycle arrest, and terminal differentiation (PMID: 27335278). | 27335278 |
DNMT3A mutant | acute myeloid leukemia | predicted - sensitive | Decitabine | Clinical Study - Cohort | Actionable | In a clinical study, acute myeloid leukemia patients harboring DNMT3A mutations demonstrated a greater complete response rate (60% vs 33%) compared to patients with wild-type DNMT3A when treated with frontline hypomethylating agents such as Dacogen (decitabine) (PMID: 27418649). | 27418649 |
DNMT3A mutant | acute myeloid leukemia | resistant | Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived acute myeloid leukemia cells harboring a DNMT3A mutation along with FLT3-ITD and NPM1 mutation were resistant to Lynparza (olaparib) in culture (PMID: 34215619). | 34215619 |
DNMT3A mutant | myelofibrosis | not applicable | N/A | Guideline | Prognostic | DNMT3A mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org). | detail... |
DNMT3A mutant | angioimmunoblastic T-cell lymphoma | not applicable | N/A | Guideline | Diagnostic | DNMT3A mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org). | detail... |