Genetic Information

Gene & Transcript Details

Gene
PIK3CA
Transcript
NM_006218.2 MANE Select
Total Exons
—
Reference Sequence
NC_000003.11
Alternative Transcripts
IDStatusDetails
NM_006218.2 Alternative 3724 nt | 158–3364
NM_006218.3 Alternative 9104 nt | 158–3364
NM_006218.4 MANE Select 9259 nt | 324–3530

Variant Details

HGVS Notation
NM_006218.2:c.93A>G
Protein Change
I31M
Location
Exon 2 (Exon 2 of )
2
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Uncertain Significance (VUS)
0 publications
Clinical Statement

"This variant has been reported in ClinVar as Uncertain Significance by ClinGen Brain Malformations Variant Curation Expert Panel expert panel."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM27376
Recurrence
2 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene PIK3CA.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: PIK3CAI31MPIK3CAI31MSomaticNCBI Gene:5290|Show additional gene information Variant OverviewPIK3CA, the catalytic subunit of PI3-kinase, is frequently mutated in a diverse range of cancers including breast, endometrial and cervical cancers.The PIK3CA I31M mutation is likely neutral.Hide mutation effect description The PIK3CA I31M mutation is located in the adaptor binding domain in exon 2 of the protein. Expression of this mutation in Ba/F3 cells or MCF10A cells demonstrated that it is likely neutral as measured by cytokine- and factor-independent proliferation comparable to wildtype PIK3CA (PMID: 26627007, 28528867, 29533785). JAX-CKB: PIK3CA I31M lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). I31M demonstrates transformation potential and ability to promote growth factor-independent cell survival at similar levels to wild-type Pik3ca protein in cell culture (PMID: 26627007, PMID: 29533785).

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 123 bp
- Donor Loss (DL) 0.02 -71 bp
+ Acceptor Gain (AG) 0.0 -168 bp
+ Donor Gain (DG) 0.06 117 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)