Gene Variant Detail

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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), and results in hypomethylation, cytokine-independent growth, increased cell proliferation and impaired differentiation in cultured cells (PMID: 31164355, PMID: 32015320).
Associated Drug Resistance

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Transcript NM_022552
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
XM_017003526 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
NM_175629 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

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive I-BET151 Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line harboring DNMT3A R882H and NRAS G12D mutations demonstrated reduced proliferation and downregulation of a DNMT3A R882H associated gene expression profile upon I-BET151 treatment in culture, and I-BET151 treatment delayed the onset of leukemia symptoms and improved survival in xenograft mouse models derived from these cells (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D was sensitive to Mekinist (trametinib), demonstrating impaired disease progression and improved survival (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive I-BET151 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D treated with combined I-BET151 and Mekinist (trametinib) demonstrated impaired disease progression and improved survival superior to either therapy alone (PMID: 31164355). 31164355
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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
Molecular Profile Protein Effect Treatment Approaches
DNMT3A R882H loss of function
DNMT3A R882H FLT3 Y599_D600insSTDNEYFYVDFREYEY NPM1 W288fs
DNMT3A R882H NRAS G12D