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LYFE SCIENCES
Project: HERA
NM_006218.4:c.335T>C
p.Ile112Thr  ·  PIK3CA
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Classification rationale
1

The PIK3CA c.335T>C (p.Ile112Thr, p.I112T) variant has not been reported in ClinVar.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting PM2_Supporting under the Brain Malformations VCEP rule for variants observed in no more than 1 person.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

The p.Ile112Thr change affects residue 112, which is outside the PIK3CA Table 4 approved kinase-domain intervals of amino acids 322-483 and 797-1068, so PM1 is not met.

cspec ↗
4

Computational data show no predicted splice impact by SpliceAI (max delta score 0.00), with REVEL 0.39 and BayesDel 0.238394, but under this VCEP PP3 is not applicable and BP4 is restricted to synonymous, intronic, or UTR variants.

spliceai ↗ cspec ↗
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
—
Research and evidence
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.39. BayesDel score = 0.238394.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant lies in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant lies in a statistically significant hotspot.
ResidueI112
Hotspots ↗