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Gene DNMT3A
Variant R882H
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions DNMT3A R882H lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R882H disrupts the tetramerization ability of the Dnmt3a protein, resulting in reduced DNA binding affinity and altered catalytic activity in in vitro assays (PMID: 22722925), disrupts Tp53 inhibition of methylation (PMID: 31640986), and results in hypomethylation, cytokine-independent growth, increased cell proliferation and impaired differentiation in cultured cells (PMID: 31164355, PMID: 32015320).
Associated Drug Resistance
Category Variants Paths

DNMT3A mutant DNMT3A inact mut DNMT3A R882H

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Transcript NM_022552.5
gDNA chr2:g.25234373C>T
cDNA c.2645G>A
Protein p.R882H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_022552.4 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
NM_175629 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
XM_017003526 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
XM_017003526.2 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
NM_175629.2 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
XM_017003526.1 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
NM_022552 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
XM_005264175.5 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
NM_175629.2 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
XM_005264175 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
XM_005264175.6 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38
NM_022552.5 chr2:g.25234373C>T c.2645G>A p.R882H RefSeq GRCh38/hg38

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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 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 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 angioimmunoblastic T-cell lymphoma not applicable N/A Guideline Diagnostic DNMT3A mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org). detail...
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