Genetic Information

Gene & Transcript Details

Gene
TET2
Transcript
NM_001127208.2 MANE Select
Total Exons
—
Reference Sequence
NC_000004.11
Alternative Transcripts
IDStatusDetails
NM_001127208.2 RefSeq Select 9796 nt | 488–6496
NM_001127208.3 MANE Select 9589 nt | 297–6305
NM_001127208.1 Alternative 9677 nt | 387–6395

Variant Details

HGVS Notation
NM_001127208.2:c.2926C>T
Protein Change
Q976*
Location
Exon 3 (Exon 3 of )
3
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.000796 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
COSM9861695
Recurrence
16 occurrences
PM1 Criteria
Not Applied
COSMIC Database 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 TET2.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: TET2Q976*TET2Q976*SomaticNCBI Gene:54790|Show additional gene information Variant OverviewTET2, a tumor suppressor and DNA demethylase, is frequently mutated in hematologic malignancies.The TET2 Q976* 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 TET2 is: Truncating mutations of TET2 disrupt the C-terminal catalytic domain of the protein, predicted to cause gene inactivation and are considered oncogenic events (PMID: 21057493, 24315485). Consequently, these alterations abrogate TET2 enzymatic function to generate 5-hydroxymethylcytosine (5-hmC) (PMID: 21057493). JAX-CKB: No results found

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

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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 -51 bp
- Donor Loss (DL) 0.01 483 bp
+ Acceptor Gain (AG) 0.01 -283 bp
+ Donor Gain (DG) 0.01 -173 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)