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
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.01 | -115 bp |
| Donor Loss (DL) | 0.1 | 8 bp |
| Acceptor Gain (AG) | 0.01 | 196 bp |
| Donor Gain (DG) | 0.02 | -2 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, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function is a known mechanism of disease." The evidence for this variant shows: "c.2782C>T (p.Q928*) is a nonsense variant in PIK3CA." Therefore, this criterion is not applied because loss of function is not an established mechanism of disease for PIK3CA.
PS1 (Not Applied)
According to VCEP guidelines, the rule for PS1 (Strong) is: "Same amino acid change as a known pathogenic variant via a different nucleotide change." The evidence for this variant shows: "This variant generates a stop codon and does not match a known pathogenic amino acid change." Therefore, this criterion is not applied because the variant does not meet PS1.
PS2 (Not Applied)
According to VCEP guidelines, the rule for PS2_Strong is: "The variant is present at a detectable allele fraction but is absent from parental samples with confirmed maternity and paternity, and is present at a detectable allele fraction in an affected tissue sample but is absent from or at a lower allelic fraction in another tissue." The evidence for this variant shows: "No de novo or mosaic parental data are available." Therefore, this criterion is not applied because de novo criteria are not met.
PS3 (Not Applied)
According to VCEP guidelines, the rule for PS3 (Strong) is: "Well-established functional studies showing a deleterious effect." The evidence for this variant shows: "No functional characterization is available for p.Q928*." Therefore, this criterion is not applied due to lack of functional evidence.
PS4 (Not Applied)
According to VCEP guidelines, the rule for PS4 is: "Statistical evidence from case-control studies or phenotype-driven point system requiring PM2." The evidence for this variant shows: "No reported cases or statistical data available." Therefore, this criterion is not applied due to absence of case-level evidence.
PM1 (Not Applied)
According to VCEP guidelines, the rule for PM1 (Supporting) is: "Residues affecting critical functional domains provided in Table 4 for each gene." The evidence for this variant shows: "p.Q928* is not located in a specified critical functional domain or hotspot." Therefore, this criterion is not applied.
PM2 (Supporting)
According to VCEP guidelines, the rule for PM2 (Supporting) is: "Absent/rare from controls in an ethnically-matched cohort population sample (≥1)." The evidence for this variant shows: "The variant is not present in gnomAD or other population databases (MAF=0)." Therefore, this criterion is applied at Supporting strength because the variant is absent from population controls.
PM3 (Not Applied)
According to standard ACMG guidelines, the rule for PM3 is: "For recessive disorders, detected in trans with a pathogenic variant." The evidence for this variant shows: "PIK3CA is not associated with a recessive phenotype and no trans data are available." Therefore, this criterion is not applied.
PM4 (Not Applied)
According to standard ACMG guidelines, the rule for PM4 is: "Protein length changes due to in-frame deletions/insertions or stop-loss variants affecting non-repeat regions." The evidence for this variant shows: "This is a stop-gain variant, which is evaluated under PVS1 if LOF is mechanism, but LOF is not established for PIK3CA." Therefore, this criterion is not applied.
PM5 (Not Applied)
According to VCEP guidelines, the rule for PM5 (Moderate) is: "Novel missense change at an amino acid residue where a different missense change is pathogenic." The evidence for this variant shows: "This is a nonsense change, not a missense variant." 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 data are available." Therefore, this criterion is not applied.
PP1 (Not Applied)
According to standard ACMG guidelines, the rule for PP1 is: "Cosegregation 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 (Not Applied)
According to VCEP guidelines, the rule for PP2 (Supporting) is: "Missense constraint with ExAC/gnomAD z-score >3.09 for specific genes." The evidence for this variant shows: "This is a nonsense variant, not a missense." Therefore, this criterion is not applied.
PP3 (Not Applied)
According to VCEP guidelines and standard ACMG, PP3 applies to variants with deleterious computational predictions. The evidence for this variant shows: "Mixed computational predictions and low CADD score, but variant is nonsense." Therefore, PP3 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 single genetic etiology." The evidence for this variant shows: "No clinical phenotype data provided." 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 but no evidence available." The evidence for this variant shows: "Not listed in ClinVar or comparable databases." Therefore, this criterion is not applied.
BA1 (Not Applied)
According to VCEP guidelines, the rule for BA1 (Stand Alone) is: "Allele frequency >0.0926%." The evidence for this variant shows: "MAF=0% in gnomAD." Therefore, this criterion is not applied.
BS1 (Not Applied)
According to VCEP guidelines, the rule for BS1 (Strong) is: "Allele frequency >0.0185%." The evidence for this variant shows: "MAF=0% in population databases." Therefore, this criterion is not applied.
BS2 (Not Applied)
According to VCEP guidelines, the rule for BS2 (Strong) is: "Observation of variant in ≥3 unaffected individuals or well-phenotyped family members." The evidence for this variant shows: "No such data are available." Therefore, this criterion is not applied.
BS3 (Not Applied)
According to VCEP guidelines, the rule for BS3 (Strong/Supporting) is: "Well-established functional studies showing 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 gene where only loss of function causes disease." The evidence for this variant shows: "This is a nonsense variant and PIK3CA disease mechanism is gain-of-function." 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 dominant gene." The evidence for this variant shows: "No trans data available." Therefore, this criterion is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines, the rule for BP3 is: "In-frame deletions/insertions in repetitive regions without predicted functional impact." The evidence for this variant shows: "This is a nonsense variant, not an in-frame indel." Therefore, this criterion is not applied.
BP4 (Not Applied)
According to VCEP guidelines, the rule for BP4 (Supporting) is: "Two out of three splicing prediction tools predict no splicing impact for synonymous, intronic or UTR variants." The evidence for this variant shows: "This is a coding nonsense variant." 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 data available." 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 without evidence." The evidence for this variant shows: "Not reported in such sources." Therefore, this criterion is not applied.
BP7 (Not Applied)
According to VCEP guidelines, the rule for BP7 (Supporting) is: "Synonymous variant at non-conserved nucleotide (PhyloP <0.1) in UTR/intronic positions." The evidence for this variant shows: "This is a nonsense variant." Therefore, this criterion is not applied.