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LYFE SCIENCES
Project: HERA
NM_001127208.2:c.3784C>T
p.Arg1262Trp  ·  TET2
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Classification rationale
1

The TET2 c.3784C>T (p.Arg1262Trp; p.R1262W) variant has not been reported in ClinVar.

clinvar ↗
2

This variant is present at low frequency in gnomAD v2.1 and v4.1, with the highest observed frequency 0.00648% (1/15,424 alleles) in European non-Finnish individuals in gnomAD v2.1, which is below the 0.1% PM2 threshold and below the BS1 (>0.3%) and BA1 (>1%) thresholds.

gnomad_v2 ↗ gnomad_v4 ↗
3

No variant-specific functional study establishing either a damaging effect or normal function was identified; the available published TET2 structural study provides protein-domain context but does not assay p.Arg1262Trp directly.

oncokb ↗ PMID:24315485 ↗
4

Computational evidence is mixed overall: SpliceAI predicts no significant splice impact (max delta score 0.02), while REVEL is 0.536 and BayesDel is 0.118577, which does not provide concordant support for either PP3 or BP4.

spliceai ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 3.18532e-05; MAF= 0.00319%, 1/31394 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.4834e-05; MAF= 0.00648%, 1/15424 alleles, homozygotes = 0).
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 4.51226e-06; MAF= 0.00045%, 7/1551328 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.44343e-05; MAF= 0.00244%, 1/40926 alleles, homozygotes = 0); grpmax FAF= 1.28e-06.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. TET2, a tumor suppressor and DNA demethylase, is frequently mutated in hematologic malignancies.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.536. BayesDel score = 0.118577.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV54399852, n = 5 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueR1262
Hotspots ↗