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.3784C>T
Protein Change
R1262W
Location
Exon 6 (Exon 6 of )
6
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.00319 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

""

COSMIC Somatic Evidence

Open
COSMIC ID
COSM5564331
Recurrence
5 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 TET2.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: TET2R1262WTET2R1262WSomaticNCBI Gene:54790|Show additional gene information Variant OverviewTET2, a tumor suppressor and DNA demethylase, is frequently mutated in hematologic malignancies.The TET2 R1262W mutation has not specifically been reviewed by the OncoKB team. While TET2 R1262A is likely neutral, the oncogenic effect of TET2 R1262W is unknown.Hide mutation effect description The TET2 R1262W mutation has not specifically been reviewed by the OncoKB team. However, the mutation effect description for TET2 R1262A, an alternate allele of TET2 R1262W, is: The TET2 R1262A mutation is located at a residue involved in the hydrogen binding of methylated cytosine (m6C) in substrate DNA. In vitro studies with HEK293T cells expressing this mutation demonstrate TET2 R1262A is likely neutral as measured by minimal effect on enzymatic activity compared to wildtype (PMID: 24315485). 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) 0.02 -80 bp
- Donor Loss (DL) 0.0 19 bp
+ Acceptor Gain (AG) 0.0 -211 bp
+ Donor Gain (DG) 0.0 1 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:
PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)