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LYFE SCIENCES
Project: HERA
NM_006218.4:c.371C>A
p.Pro124Gln  ·  PIK3CA
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Classification rationale
1

The PIK3CA c.371C>A (p.Pro124Gln; p.P124Q) variant has been observed in somatic cancer knowledgebases and is absent from ClinVar.

oncokb ↗ clinvar ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting PM2 at Supporting strength under the Brain Malformations VCEP specification.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

Available reviewed functional evidence did not provide directly confirmed assay-level results for p.Pro124Gln that met VCEP requirements for applying either PS3 or BS3 in this pass.

oncokb ↗ PMID:22430209 ↗ cspec ↗
4

Computational data show REVEL 0.237, BayesDel 0.018, and SpliceAI max delta 0.05; however, PP3 is not applicable and BP4 is restricted to synonymous, intronic, or UTR splicing contexts in this VCEP.

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: Likely Oncogenic
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.237. BayesDel score = 0.018.
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; COSV55927445, n = 3 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueP124
Hotspots ↗