PIK3CA c.1233C>A, p.Gly411=
NM_006218.4:c.1233C>A
Population Frequency
0.0 in 100,000
Rare
ClinVar Classification
Unknown
0 publications
REVEL Score
N/A
Not Available
COSMIC Recurrence
0 occurrences
No Criteria Applied
Classification Evidence
Detailed Information
Genetic Information
Gene & Transcript Details
Gene
PIK3CA
Transcript
NM_006218.4
MANE Select
Total Exons
21
Strand
Forward (+)
Reference Sequence
NC_000003.11
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_006218.2 | Alternative | 21 exons | Forward |
| NM_006218.3 | Alternative | 21 exons | Forward |
Variant Details
HGVS Notation
NM_006218.4:c.1233C>A
Protein Change
G411=
Location
Exon 7
(Exon 7 of 21)
5'
Exon Structure (21 total)
3'
Functional Consequence
Loss of Function
Related Variants
Variant interpretation based on transcript NM_006218.4
Clinical Evidence
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.0005%
0.001%
0.01%
0.05%
1%+
ACMG Criteria Applied
PM2
This variant is not present in gnomAD (PM2 criteria applies).
Classification
Unknown
Publications
0 publications
Clinical Statement
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
Functional Studies
Computational Evidence
Pathogenicity Predictions
Predictor Consensus
Mixed/VUS
PP3 Applied
No
Additional Predictors
Benign:
CADD: 0.69
VCEP Guidelines
Applied ACMG/AMP Criteria
VCEP Guidelines
PVS1
PVS1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PVS1 is: 'Null variant (nonsense, frameshift, canonical +1/+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: NM_006218.4:c.1233C>A is a synonymous change (Gly411Gly) and does not produce a null allele. Therefore, PVS1 is not applied (Not Applied) because the variant does not result in loss-of-function.
PS1
PS1 (Not Applied)
Strength Modified
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: no amino acid change (synonymous). Therefore, PS1 is not applied (Not Applied) because there is no altered amino acid.
PS2
PS2 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for PS2 (Strong) is: 'Award the PS2_Strong point if Criteria 1 AND Criteria 2 are fulfilled (de novo in proband with confirmed maternity and paternity and variant allele fraction criteria).' The evidence for this variant shows: no de novo or tissue-specific high-confidence somatic data. Therefore, PS2 is not applied (Not Applied) due to lack of de novo evidence.
PS3
PS3 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for PS3 is: 'Award PS3 if the functional assay meets the acceptability criteria delimited in (PMID: 31892348) with specifications added by the VCEP.' The evidence for this variant shows: no functional studies have been performed. Therefore, PS3 is not applied (Not Applied) because functional data are missing.
PS4
PS4 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for PS4 (Very Strong/Strong/Moderate/Supporting) is: 'Points are assigned for phenotype according to Table 2A and Table 2B for case-level data in the literature, applicable only if PM2 is met.' The evidence for this variant shows: no case-level phenotype data are available. Therefore, PS4 is not applied (Not Applied) due to absence of clinical case reports.
PM1
PM1 (Not Applied)
Strength Modified
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: it is a synonymous change not affecting an amino acid residue. Therefore, PM1 is not applied (Not Applied).
PM2
PM2 (Supporting)
Strength Modified
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: it is absent (MAF=0%) from gnomAD, 1000 Genomes, and other population databases. Therefore, PM2 is applied at Supporting strength because the variant is not found in controls.
PM3
PM3 (Not Applied)
Strength Modified
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: no data on trans configuration or recessive inheritance. Therefore, PM3 is not applied (Not Applied).
PM4
PM4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM4 is: 'Protein length changes due to in-frame indels or stop-loss variants.' The evidence for this variant shows: it is synonymous and does not alter protein length. Therefore, PM4 is not applied (Not Applied).
PM5
PM5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM5 is: 'Novel missense change at an amino acid residue where a different missense change is pathogenic.' The evidence for this variant shows: no amino acid change (synonymous). Therefore, PM5 is not applied (Not Applied).
PM6
PM6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM6 is: 'Assumed de novo, without confirmation of paternity and maternity.' The evidence for this variant shows: no de novo data. Therefore, PM6 is not applied (Not Applied).
PP1
PP1 (Not Applied)
Strength Modified
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. Therefore, PP1 is not applied (Not Applied).
PP2
PP2 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for PP2 (Supporting) is: 'Missense constraint z-score >3.09 for applicable genes.' The evidence for this variant shows: it is synonymous, not missense. Therefore, PP2 is not applied (Not Applied).
PP3
PP3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PP3 is: 'Multiple lines of computational evidence support a deleterious effect.' The evidence for this variant shows: computational tools (CADD score 0.69, SpliceAI 0) predict no impact. Therefore, PP3 is not applied (Not Applied) because there is no in silico evidence of deleteriousness.
PP4
PP4 (Not Applied)
Strength Modified
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 phenotype data. Therefore, PP4 is not applied (Not Applied).
PP5
PP5 (Not Applied)
Strength Modified
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 databases. Therefore, PP5 is not applied (Not Applied).
BA1
BA1 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for BA1 (Stand Alone) is: 'Allele frequency >0.0926%.' The evidence for this variant shows: MAF=0% in population databases. Therefore, BA1 is not applied (Not Applied).
BS1
BS1 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for BS1 (Strong) is: 'Allele frequency >0.0185%.' The evidence for this variant shows: absent from population cohorts. Therefore, BS1 is not applied (Not Applied).
BS2
BS2 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for BS2 (Strong) is: '≥3 homozygotes in gnomAD or ≥3 heterozygotes in well-phenotyped family members.' The evidence for this variant shows: no such observations. Therefore, BS2 is not applied (Not Applied).
BS3
BS3 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for BS3 is: 'Well-established functional studies show no damaging effect.' The evidence for this variant shows: no functional studies exist. Therefore, BS3 is not applied (Not Applied).
BS4
BS4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BS4 is: 'Lack of segregation in affected family members.' The evidence for this variant shows: no segregation data. Therefore, BS4 is not applied (Not Applied).
BP1
BP1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP1 is: 'Missense variant in a gene where only truncating variants cause disease.' The evidence for this variant shows: it is synonymous. Therefore, BP1 is not applied (Not Applied).
BP2
BP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP2 is: 'Observed in trans with a pathogenic variant.' The evidence for this variant shows: no data on cis/trans observation. Therefore, BP2 is not applied (Not Applied).
BP3
BP3 (Not Applied)
Strength Modified
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: it is a single-nucleotide synonymous change. Therefore, BP3 is not applied (Not Applied).
BP4
BP4 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for BP4 (Supporting) is: 'Award BP4 for a synonymous variant if two of three splicing prediction tools (varSEAK, SpliceAI, MaxEntScan) predict no impact on splicing.' The evidence for this variant shows: only SpliceAI predicts no impact; results from the other two tools are unavailable. Therefore, BP4 is not applied (Not Applied) due to insufficient splicing prediction data.
BP5
BP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP5 is: 'Variant found in a case with an alternate molecular cause for disease.' The evidence for this variant shows: no such case data. Therefore, BP5 is not applied (Not Applied).
BP6
BP6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP6 is: 'Reputable source reports variant as benign.' The evidence for this variant shows: not reported benign. Therefore, BP6 is not applied (Not Applied).
BP7
BP7 (Not Applied)
Strength Modified
According to VCEP guidelines, the rule for BP7 (Supporting) is: 'For synonymous variants, if the nucleotide is non-conserved (PhyloP score <0.1).' The evidence for this variant shows: conservation data (PhyloP) are unavailable. Therefore, BP7 is not applied (Not Applied).