Genetic Information

Gene & Transcript Details

Gene
DNMT3A
Transcript
NM_022552.4 MANE Select
Total Exons
—
Reference Sequence
NC_000002.11
Alternative Transcripts
IDStatusDetails
NM_022552.4 RefSeq Select 4324 nt | 268–3006
NM_022552.5 MANE Select 9421 nt | 278–3016
NM_022552.3 Alternative 4314 nt | 258–2996

Variant Details

HGVS Notation
NM_022552.4:c.1312dup
Protein Change
D438Gfs*7
Location
Exon 11 (Exon 11 of )
11
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Unknown
0 publications
Clinical Statement

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COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene DNMT3A.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: DNMT3AD438Gfs*7DNMT3AD438Gfs*7SomaticNCBI Gene:1788|Show additional gene information Variant OverviewDNMT3A, a tumor suppressor and DNA methyltransferase, is recurrently mutated in acute myeloid leukemia and other hematologic malignancies.The DNMT3A D438Gfs*7 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in DNMT3A is: Truncating mutations in DNMT3A have been detected in patients with acute myeloid leukemia (AML) and developmental overgrowth disorders (PMID: 25964253, 24614070). These alterations are predicted to cause nonsense-mediated decay and haploinsufficiency, and are associated with a better survival and lower relapse risk in AML (PMID: 25964253). Give the role of DNMT3A in DNA methylation, loss results in disturbed methylation patterns and global hypomethylation, which is required for transcription of lineage-specific programs in myeloid development (PMID: 21067377). JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Unknown
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.04 30 bp
- Donor Loss (DL) 0.06 -85 bp
+ Acceptor Gain (AG) 0.0 -48 bp
+ Donor Gain (DG) 0.0 -228 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PVS1

PVS1 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)