About PIK3R1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PIK3R1 c.1585_1587del, p.(Asp529del)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen PIK3R1 VCEP v1.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 0
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_181523.2:c.1585_1587del (p.Asp529del) is absent from all gnomAD population databases (v2.1, v4.1, Canada), satisfying the VCEP PM2_Supporting threshold of total allele frequency < 0.00000132 across all populations.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
ClinGen Antibody Deficiencies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PIK3R1 Version 1.0 v1.0 point-based framework: PM2 supporting (+1) = 1 points, which maps to VUS.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
No screenshot for this evidence
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PIK3R1, the regulatory subunit of PI3-kinase, is mutated in various cancers, most frequently in glioma, endometrial and colorectal cancers.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV109582795, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PIK3R1 VCEP v1.0, with the data and sources behind each one.
28 criteria with recorded statuses: 1 met · 6 not met · 8 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_181523.2:c.1585_1587del (p.Asp529del) is absent from all gnomAD population databases, fulfilling VCEP PM2_Supporting (AF < 0.00000132).
No other pathogenic or benign criteria were met under the Antibody Deficiencies VCEP specifications for PIK3R1. The variant is an in-frame deletion of a single amino acid in exon 13 (iSH2 domain) and is not predicted to alter splicing (SpliceAI max delta = 0.00).
With a single supporting-level pathogenic criterion (PM2_Supporting = +1 Bayesian point), the variant falls in the Uncertain Significance range (0-5 points) under the Tavtigian 2020 Bayesian point scale adopted by the VCEP.
No criteria match.
Met · 1
PM2 SupportingNM_181523.2:c.1585_1587del (p.Asp529del) is absent from all gnomAD population databases (v2.1, v4.1, Canada), satisfying the VCEP PM2_Supporting threshold of total allele frequency < 0.00000132 across all populations. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes)
- Absent from gnomAD v4.1 (exomes)
- Absent from gnomAD-Canada v1.0 (genomes)
- Allele frequency effectively 0
- well below VCEP PM2_Supporting threshold of 0.00000132
Sources
Not met · 6 · evaluated, threshold not reached
PM4 VCEP PM4 requires an in-frame deletion resulting in a protein length change of ≥2 amino acids. This variant deletes a single amino acid (p.Asp529del) and does not meet the ≥2 amino acid threshold. Details ▾Hide ▴
Evidence considered
- In-frame deletion of 3 nucleotides removes 1 amino acid (p.Asp529del)
- VCEP PM4 threshold requires ≥2 amino acid change
Sources
PP3 VCEP PP3 criteria are: (1) missense variant with REVEL ≥0.644 and CADD ≥26.0 — not applicable for this in-frame deletion; (2) missense, synonymous, or intronic variants with SpliceAI Δ ≥0.2 — not applicable as this is an in-frame deletion, and SpliceAI max delta is 0.00 anyway. Details ▾Hide ▴
Evidence considered
- In-frame deletion
- not missense/synonymous/intronic — PP3 SpliceAI pathway not applicable
- SpliceAI max delta score = 0.00 — no splice alteration predicted
- REVEL and CADD not available for indels
Sources
BA1 Variant is absent from gnomAD (v2.1, v4.1, Canada). Does not meet the VCEP BA1 threshold of GrpMax filtering allele frequency ≥0.00316. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 and v4.1
- Allele frequency 0.0
- below BA1 threshold of 0.00316
Sources
BS1 Variant is absent from gnomAD (v2.1, v4.1, Canada). Does not meet the VCEP BS1 threshold of GrpMax filtering allele frequency ≥0.000316. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 and v4.1
- Allele frequency 0.0
- below BS1 threshold of 0.000316
Sources
BP4 VCEP BP4 is met by: (1) missense variants with REVEL ≤0.290 and CADD ≤21.5 and all SpliceAI Δ <0.1, or (2) synonymous/intronic variants without splice impact. This is an in-frame deletion and is not covered by either BP4 pathway. Although SpliceAI max delta is 0.00, the VCEP does not provide a BP4 rule for in-frame deletions. Details ▾Hide ▴
Evidence considered
- In-frame deletion — not covered by VCEP BP4 missense or synonymous/intronic pathways
- SpliceAI max delta = 0.00
- no splice impact
Sources
BP7 VCEP BP7 applies to synonymous variants (except first/last 3 nucleotides of exon) or intronic variants (outside +1 to +6 and -1 to -20 positions) without splice impact. This is an in-frame deletion, not covered by BP7. Details ▾Hide ▴
Evidence considered
- In-frame deletion — not covered by VCEP BP7 synonymous/intronic pathways
Sources
Not assessed · 8 · no assessment recorded
PS2 No de novo observation with confirmed maternity and paternity has been reported for this variant. No proband meeting VCEP PS2 phenotype scoring criteria is available. Details ▾Hide ▴
Still missing
- No de novo data available for this variant
PS3 No functional studies directly testing NM_181523.2:c.1585_1587del (p.Asp529del) were identified in the literature or in the VCEP-approved functional assay compendium (04_08_26_PIK3R1_Functional_Assays_PS3_BS3.xlsx). The VCEP catalogs approved assay types (AKT kinase activity, lipid kinase activity, protein binding, conformational dynamics) but this specific variant was not tested in any of them. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet reviewed — catalogs approved assay types but does not list p.Asp529del as tested
- No PMIDs identified for this variant in literature_pass
Still missing
- No variant-specific functional data available
Sources
vcep_04_08_26_pik3r1_functional_assays_ps3_bs3
PS4 No probands with this variant meeting the VCEP PS4 phenotype scoring criteria (≥6 points) and PIK3CD genotyping requirements have been identified in the available evidence. Details ▾Hide ▴
Evidence considered
- Variant is absent from ClinVar
- no proband-level data available
Still missing
- No proband data available for this variant
PP1 No co-segregation data is available for this variant. No family studies with affected relatives meeting VCEP PP1 phenotype scoring criteria have been identified. Details ▾Hide ▴
Still missing
- No co-segregation or family data available
PP4 No proband phenotype data meeting the VCEP PP4 threshold (≥10 phenotype points with PIK3CD genotyping) is available for this variant. Details ▾Hide ▴
Still missing
- No proband phenotype data available
BS3 No functional studies showing a non-damaging effect for p.Asp529del were identified. The VCEP-approved functional assay compendium was reviewed but this variant was not tested in any approved assay. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet reviewed
- p.Asp529del not listed as tested
- No variant-specific functional data available
Still missing
- No variant-specific functional data available
Sources
vcep_04_08_26_pik3r1_functional_assays_ps3_bs3
BS4 No segregation data showing affected family members lacking the variant is available. VCEP BS4 requires at least one affected family member without the variant scoring ≥6 phenotype points. Details ▾Hide ▴
Still missing
- No family segregation data available
BP5 No cases with an alternative molecular basis for disease have been identified for this variant. VCEP BP5 requires at least 2 such cases. Details ▾Hide ▴
Still missing
- No alternative molecular basis cases identified
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_181523.2:c.1585_1587del (p.Asp529del) is an in-frame deletion of a single amino acid in exon 13. It does not introduce a premature termination codon, is not predicted to trigger nonsense-mediated decay, and does not disrupt canonical splice sites. Does not meet any VCEP PVS1 strength rule (which requires nonsense/frameshift variants with NMD or canonical splice variants causing exon skipping). Details ▾Hide ▴
Evidence considered
- In-frame deletion of 1 amino acid (p.Asp529del) in exon 13 of NM_181523.2
- SpliceAI max delta score = 0.00
- no splice impact predicted
- VCEP PVS1 rules require nonsense/frameshift with NMD or canonical splice disruption — not met
Sources
pvs1_variant_assessmentcspec ↗
PS1 N/AVCEP PS1 applies to missense variants with the same amino acid change as a previously classified pathogenic/likely pathogenic variant, or to canonical splice variants with equivalent predicted impact. This variant is an in-frame deletion, not a missense or splice variant. Details ▾Hide ▴
Evidence considered
- Variant is an in-frame deletion (p.Asp529del)
- not a missense substitution
- SpliceAI max delta = 0.00
- no splice-altering prediction applicable
Sources
PM1 VCEPPM1 is marked as not applicable by the Antibody Deficiencies VCEP for PIK3R1. Details ▾Hide ▴
PM5 N/AVCEP PM5 applies only to missense variants at the same codon with a comparator classified as Pathogenic/Likely Pathogenic by VCEP standards. This is an in-frame deletion, not a missense variant. The pm5_candidates assessment confirms the variant is not eligible for classic PM5. Details ▾Hide ▴
Evidence considered
- Variant class is deletion
- not missense — PM5 not applicable per VCEP rules
- pm5_candidates recommendation: not_applicable
Sources
cspec ↗pm5_candidates
PM6 VCEPPM6 is marked as not applicable by the Antibody Deficiencies VCEP for PIK3R1. VCEP instructs use of PS2 instead for de novo evidence. Details ▾Hide ▴
PP2 VCEPPP2 is marked as not applicable by the Antibody Deficiencies VCEP for PIK3R1. The gnomAD v2.1.1 missense Z-score for PIK3R1 (Z = 2.72) does not support constraint for missense variation. Details ▾Hide ▴
PP5 VCEPPP5 is marked as not applicable for this VCEP by the Antibody Deficiencies Expert Panel. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: PP5 applicability = 'Not Applicable for this VCEP'
Sources
BS2 VCEPBS2 is marked as not applicable by the Antibody Deficiencies VCEP for PIK3R1 due to incomplete penetrance and variable expressivity of disease. Details ▾Hide ▴
BP1 VCEPBP1 is marked as not applicable by the Antibody Deficiencies VCEP for PIK3R1. Pathogenic PIK3R1 variants are not limited to truncating variants — missense variants are also pathogenic. Details ▾Hide ▴
BP2 VCEPBP2 is marked as not applicable by the Antibody Deficiencies VCEP for PIK3R1. Allelic mechanisms are incompletely understood, and the possibility of diverse combinatorial variant effects cannot be excluded. Details ▾Hide ▴
BP3 VCEPBP3 is marked as not applicable by the Antibody Deficiencies VCEP for PIK3R1 — repetitive regions of unknown function are not known within PIK3R1. Details ▾Hide ▴
BP6 VCEPBP6 is marked as not applicable for this VCEP. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: BP6 applicability = 'Not Applicable for this VCEP'
Sources
PS5 N/APS5 is not a recognized ACMG/AMP 2015 criterion and is not defined in the PIK3R1 Antibody Deficiencies VCEP specification. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- PIK3R1
- Transcript
- NM_181523.2
- Coding (HGVS c.)
- NM_181523.2:c.1585_1587del
- Protein (HGVS p.)
- NP_852664.1:p.(Asp529del)
- GRCh38
- chr5:68295161 TATG>T
- GRCh37
- chr5:67590989 TATG>T
- COSMIC
- COSV109582795
Gene diagram
Every interpreted variant in PIK3R1, mapped onto the exon structure of NM_181523.2. Select a row to find it on the plot.
PIK3R1NM_181523.2
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PIK3R1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 VCEP PP3 criteria are: (1) missense variant with REVEL ≥0.644 and CADD ≥26.0 — not applicable for this in-frame deletion; (2) missense, synonymous, or intronic variants with SpliceAI Δ ≥0.2 — not applicable as this is an in-frame deletion, and SpliceAI max delta is 0.00 anyway. Details ▾Hide ▴
Evidence considered
- In-frame deletion
- not missense/synonymous/intronic — PP3 SpliceAI pathway not applicable
- SpliceAI max delta score = 0.00 — no splice alteration predicted
- REVEL and CADD not available for indels
Sources
BP4 VCEP BP4 is met by: (1) missense variants with REVEL ≤0.290 and CADD ≤21.5 and all SpliceAI Δ <0.1, or (2) synonymous/intronic variants without splice impact. This is an in-frame deletion and is not covered by either BP4 pathway. Although SpliceAI max delta is 0.00, the VCEP does not provide a BP4 rule for in-frame deletions. Details ▾Hide ▴
Evidence considered
- In-frame deletion — not covered by VCEP BP4 missense or synonymous/intronic pathways
- SpliceAI max delta = 0.00
- no splice impact
Sources
BP7 VCEP BP7 applies to synonymous variants (except first/last 3 nucleotides of exon) or intronic variants (outside +1 to +6 and -1 to -20 positions) without splice impact. This is an in-frame deletion, not covered by BP7. Details ▾Hide ▴
Evidence considered
- In-frame deletion — not covered by VCEP BP7 synonymous/intronic pathways
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1626566541
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_181523.2%3Ac.1585_1587del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/5-67590989-TATG-T?dataset=gno…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr5-68295161-TATG-T?dataset=…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/5-68295161-TATG-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_181523.2%3Ac.1585…
- OncoKB ↗www.oncokb.org/gene/PIK3R1/D529del
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=185444707
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PIK3R1, the regulatory subunit of PI3-kinase, is mutated in various cancers, most frequently in glioma, endometrial and colorectal cancers.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV109582795, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.