Genetic Information

Gene & Transcript Details

Gene
EZH2
Transcript
NM_004456.4 MANE Select
Total Exons
—
Reference Sequence
NC_000007.13
Alternative Transcripts
IDStatusDetails
NM_004456.4 RefSeq Select 2723 nt | 194–2449
NM_004456.3 Alternative 2695 nt | 167–2422
NM_004456.5 MANE Select 2654 nt | 136–2391

Variant Details

HGVS Notation
NM_004456.4:c.1797G>A
Protein Change
W599*
Location
Exon 15 (Exon 15 of )
15
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
Uncertain Significance (VUS)
1 publications
Clinical Statement

"This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratories)."

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 EZH2.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: EZH2W599*EZH2W599*SomaticNCBI Gene:2146|Show additional gene information Variant OverviewEZH2, an epigenetic modifier, is altered by mutation and/or overexpression in solid tumors and hematologic malignancies.The EZH2 W599* is a truncating mutation; truncating mutations in this gene are considered likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in EZH2 is: EZH2 truncating mutations can produce several forms of C-terminally truncated proteins. These mutations have been found in myelodysplastic syndromes (PMID: 20601954). EZH2 loss in hematopoietic stem cells results in defective differentiation (PMID: 27926872). Patients harboring EZH2 truncating mutations have exhibited biallelic mutation or loss of heterozygosity at the EZH2 locus (PMID: 20601954). 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
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 -6 bp
- Donor Loss (DL) 0.0 -54 bp
+ Acceptor Gain (AG) 0.01 172 bp
+ Donor Gain (DG) 0.0 125 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)