Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| 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
Clinical & Population Data
Population Frequency
gnomADClinVar
Open""
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
The PIK3CA L62I variant has not been functionally characterized, and its biological significance remains unknown.
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Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | -259 bp |
| Donor Loss (DL) | 0.04 | 26 bp |
| Acceptor Gain (AG) | 0.03 | 32 bp |
| Donor Gain (DG) | 0.01 | -162 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to standard ACMG guidelines, the rule for PVS1 is: "Null Variant (nonsense, fs, start codon, splicing +1/2, startgain, single or multi-exon deletion) in a gene where LOF is a known mechanism of disease". The evidence for this variant shows: it is a missense change (L62I), not a null variant. Therefore, this criterion is not applied.
PS1 (Not Applied)
According to standard ACMG guidelines, the rule for PS1 is: "Same amino acid change as a previously established pathogenic variant regardless of nucleotide change". The evidence for this variant shows: there is no previously established pathogenic variant causing L62I. Therefore, this criterion is not applied.
PS2 (Not Applied)
According to standard ACMG guidelines, the rule for PS2 is: "De novo (both maternity and paternity confirmed) in a patient with the disease and no family history". The evidence for this variant shows: no de novo data are available. Therefore, this criterion is not applied.
PS3 (Not Applied)
According to standard ACMG guidelines, the rule for PS3 is: "Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product". The evidence for this variant shows: no functional characterization studies have been performed. Therefore, this criterion is not applied.
PS4 (Not Applied)
According to VCEP guidelines, the rule for PS4 is: "Phenotype criteria can only be used if the variant is absent/rare from controls according to PM2; strength of evidence is determined by points according to case reports". The evidence for this variant shows: no case or phenotype data are available. Therefore, this criterion is not applied.
PM1 (Not Applied)
According to VCEP guidelines, the rule for PM1 is: "Supporting: Residues affecting critical functional domains provided in Table 4 for each gene". The evidence for this variant shows: residue L62 is not within a critical functional domain or known hotspot. Therefore, this criterion is not applied.
PM2 (Supporting)
According to VCEP guidelines, the rule for PM2 is: "Supporting: Absent/rare from controls in an ethnically-matched cohort population sample (≥1)". The evidence for this variant shows: it is absent from gnomAD and other large population databases (MAF = 0%). Therefore, this criterion is applied at Supporting strength.
PM3 (Not Applied)
According to standard ACMG guidelines, the rule for PM3 is: "For recessive disorders, detected in trans with a pathogenic variant in affected individuals". The evidence for this variant shows: no data on trans occurrence with another variant. Therefore, this criterion is not applied.
PM4 (Not Applied)
According to standard ACMG guidelines, the rule for PM4 is: "Protein length changes as a result of in-frame deletions/insertions in a non-repeat region or stop-loss variants". The evidence for this variant shows: it is a single amino acid change without length alteration. Therefore, this criterion is not applied.
PM5 (Not Applied)
According to VCEP guidelines, the rule for PM5 is: "Moderate: novel missense change at an amino acid residue where a different missense change is pathogenic". The evidence for this variant shows: no pathogenic variants have been reported at residue L62. Therefore, this criterion is not applied.
PM6 (Not Applied)
According to standard ACMG guidelines, the rule for PM6 is: "Assumed de novo, but without confirmation of paternity and maternity". The evidence for this variant shows: no de novo information. Therefore, this criterion is not applied.
PP1 (Not Applied)
According to standard ACMG guidelines, the rule for PP1 is: "Co-segregation with disease in multiple affected family members". The evidence for this variant shows: no segregation data are available. Therefore, this criterion is not applied.
PP2 (Supporting)
According to VCEP guidelines, the rule for PP2 is: "Supporting: Missense constraint computed in ExAC/gnomAD was utilized. Award PP2 if the z-score > 3.09". The evidence for this variant shows: PIK3CA has a missense z-score > 3.09 and this is a missense change. Therefore, this criterion is applied at Supporting strength.
PP3 (Not Applied)
According to standard ACMG guidelines, the rule for PP3 is: "Multiple lines of computational evidence support a deleterious effect on the gene or gene product". The evidence for this variant shows: in silico predictions are mixed and inconclusive. Therefore, this criterion is not applied.
PP4 (Not Applied)
According to standard ACMG guidelines, the rule for PP4 is: "Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology". The evidence for this variant shows: no specific phenotype data. Therefore, this criterion is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines, the rule for PP5 is: "Reputable source reports variant as pathogenic". The evidence for this variant shows: not reported in ClinVar or other expert-reviewed databases. Therefore, this criterion is not applied.
BA1 (Not Applied)
According to VCEP guidelines, the rule for BA1 is: "Stand Alone: Allele frequency (>0.0926%)". The evidence for this variant shows: absent from population databases. Therefore, this criterion is not applied.
BS1 (Not Applied)
According to VCEP guidelines, the rule for BS1 is: "Strong: Allele frequency (>0.0185%)". The evidence for this variant shows: absent from controls. Therefore, this criterion is not applied.
BS2 (Not Applied)
According to VCEP guidelines, the rule for BS2 is: "Strong: ≥3 homozygotes in gnomAD or ≥3 heterozygotes in well-phenotyped family members". The evidence for this variant shows: no such observations. Therefore, this criterion is not applied.
BS3 (Not Applied)
According to VCEP guidelines, the rule for BS3 is: "Strong: Well-established functional studies show no damaging effect". The evidence for this variant shows: no functional studies available. Therefore, this criterion is not applied.
BS4 (Not Applied)
According to standard ACMG guidelines, the rule for BS4 is: "Lack of segregation in affected members of a family". The evidence for this variant shows: no segregation data. Therefore, this criterion is not applied.
BP1 (Not Applied)
According to standard ACMG guidelines, the rule for BP1 is: "Missense variant in a gene for which primarily truncating variants cause disease". The evidence for this variant shows: PIK3CA disease mechanism is gain-of-function missense, not truncating. Therefore, this criterion is not applied.
BP2 (Not Applied)
According to standard ACMG guidelines, the rule for BP2 is: "Observed in trans with a pathogenic variant for a fully penetrant dominant gene". The evidence for this variant shows: no such observations. Therefore, this criterion is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines, the rule for BP3 is: "In-frame deletions/insertions in a repetitive region without a known function". The evidence for this variant shows: not an indel. Therefore, this criterion is not applied.
BP4 (Not Applied)
According to VCEP guidelines, the rule for BP4 is: "Supporting: applicable only to synonymous, intronic (non-canonical) or UTR variants when two of three splicing tools predict no impact". The evidence for this variant shows: it is a missense change, not eligible for BP4. Therefore, this criterion is not applied.
BP5 (Not Applied)
According to standard ACMG guidelines, the rule for BP5 is: "Variant found in a case with an alternate molecular basis for disease". The evidence for this variant shows: no such case data. Therefore, this criterion is not applied.
BP6 (Not Applied)
According to standard ACMG guidelines, the rule for BP6 is: "Reputable source reports variant as benign". The evidence for this variant shows: no such reports. Therefore, this criterion is not applied.
BP7 (Not Applied)
According to VCEP guidelines, the rule for BP7 is: "Supporting: applicable only to synonymous, intronic (non-canonical) or UTR variants with low conservation". The evidence for this variant shows: it is a missense change. Therefore, this criterion is not applied.