Starting

Initialising…

PIK3CA

Final classification

VUS

PIK3CA c.371C>A · p.Pro124Gln

PIK3CA

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

Gene

PIK3CA

Transcript

NM_006218.4

HGVS · transcript:coding

NM_006218.4:c.371C>A

Consequence

N/A

GRCh38

chr3:179199708 C>A

GRCh37

chr3:178917496 C>A

Basis Brain Malformations Specification Tavtigian point framework v1.1.0 point-based framework: PM2 supporting (+1) = 1 points, which maps to VUS. ▾

Brain Malformations Specification Tavtigian point framework v1.1.0 point-based framework: PM2 supporting (+1) = 1 points, which maps to VUS.

Classification rationale

PM2 VUS

PIK3CA c.371C>A

The PIK3CA c.371C>A (p.Pro124Gln; p.P124Q) variant has been observed in somatic cancer knowledgebases and is absent from ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting PM2 at Supporting strength under the Brain Malformations VCEP specification.² 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.³ 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.⁴

PM2 → VUS

1 oncokb ↗clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗

3 oncokb ↗PMID:22430209 ↗cspec ↗

4 revelbayesdelspliceai ↗cspec ↗

Gene diagram · NM_006218.4 · variants mapped to exon structure

PIK3CA NM_006218.4

Fetching transcript structure from UCSC…

Applied criteria · 1 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

Absent from gnomAD v4.1.

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

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 ↗

Functional 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 ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

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).

Hotspots

This variant does not lie in a statistically significant hotspot.

COSMIC ↗ Hotspots ↗

Sources & reference links

8Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots