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LYFE SCIENCES
Project: HERA
NM_006218.4:c.1265del
p.Leu422TrpfsTer6  ·  PIK3CA
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Classification rationale
1

The PIK3CA c.1265del (p.(Leu422TrpfsTer6)) variant has not been reported in ClinVar.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting PM2 at Supporting strength, and its observed population frequency of 0% is below the VCEP BS1 threshold of >0.0185% and BA1 threshold of >0.0926%.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

The altered residue lies within the approved PIK3CA kinase-domain interval spanning amino acids 322-483, which is a Brain Malformations VCEP critical functional domain and supports PM1_Supporting.

cspec ↗
4

SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.07, although computational pathogenicity criteria are not applied for PIK3CA gain-of-function interpretation in this VCEP framework.

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
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Research and evidence
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).
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; COSV104381249, n = 1 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueL422
Hotspots ↗