About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.802-29C>A, p.?
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 PTEN VCEP v3.2. 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: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 and v4.1 (0/1,512,514 alleles across all populations). The PTEN VCEP specifies PM2 at supporting strength when allele frequency is <0.001% (0.00001). The observed AF of 0 satisfies this threshold.
Benign criteria applied · 1
BP7Supporting
BP7 · supporting
This is an intronic variant at c.802-29, which is beyond the -21 position from the exon 8 splice acceptor. SpliceAI predicts no impact to the splice consensus sequence and no creation of a new splice site (max delta 0.01, with individual delta scores: DS_AG=0.0, DS_AL=0.01, DS_DG=0.01, DS_DL=0.0). The PTEN VCEP BP7 applies at supporting level for intronic variants at or beyond +7/-21 where splicing prediction algorithms predict no impact.
Recorded classification: Uncertain significance
ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.2 v3.2 criteria-combination framework was evaluated deterministically with applied criteria: PM2 supporting, BP7 supporting benign; no rule matched the adjudicated criteria.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
0 / 1,512,514 alleles
gnomAD v4.1: 0 / 1,512,514 alleles. Recorded AF 0. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PTEN VCEP v3.2, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 14 not met · 0 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000314.8:c.802-29C>A is absent from gnomAD v4.1 (0/1,512,514 alleles) and gnomAD v2.1, satisfying PM2 at supporting strength per the PTEN VCEP threshold of <0.001% allele frequency.
This intronic variant at position -29 from the exon 8 acceptor splice site is at or beyond the -21 threshold. SpliceAI predicts no splicing impact (max delta 0.01; DS_AG=0.0, DS_AL=0.01, DS_DG=0.01, DS_DL=0.0), satisfying BP7 at supporting strength per the PTEN VCEP.
No pathogenic or benign criteria at moderate or higher strength are met. With one pathogenic supporting criterion (PM2_Supporting) and one benign supporting criterion (BP7), the variant is classified as a Variant of Uncertain Significance (VUS).
The variant has not been reported in ClinVar, COSMIC, or the published literature. No functional studies, segregation data, de novo observations, or case-control data are available.
No criteria match.
Met · 2
PM2 SupportingThis variant is absent from gnomAD v2.1 and v4.1 (0/1,512,514 alleles across all populations). The PTEN VCEP specifies PM2 at supporting strength when allele frequency is <0.001% (0.00001). The observed AF of 0 satisfies this threshold. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes)
- Absent from gnomAD v4.1: 0/1
- 512
- 514 alleles
- AF = 0.00000%
- homozygotes = 0
- Absent from all subpopulations including NFE (0/1
- 132
- 696)
- AFR (0/59
- 236)
- EAS (0/40
- 308)
- SAS (0/78
- 542)
Sources
BP7 SupportingThis is an intronic variant at c.802-29, which is beyond the -21 position from the exon 8 splice acceptor. SpliceAI predicts no impact to the splice consensus sequence and no creation of a new splice site (max delta 0.01, with individual delta scores: DS_AG=0.0, DS_AL=0.01, DS_DG=0.01, DS_DL=0.0). The PTEN VCEP BP7 applies at supporting level for intronic variants at or beyond +7/-21 where splicing prediction algorithms predict no impact. Details ▾Hide ▴
Evidence considered
- Intronic variant at c.802-29 (beyond -21 from exon 8 splice acceptor)
- SpliceAI max delta 0.01 (DS_AG=0.0
- DS_AL=0.01
- DS_DG=0.01
- DS_DL=0.0) — no splice impact predicted
Sources
Not met · 14 · evaluated, threshold not reached
PS2 No de novo observations have been reported for this variant. The variant is absent from ClinVar and no literature reports de novo occurrence in a patient with PHTS and no family history. Details ▾Hide ▴
Evidence considered
- Variant absent from ClinVar
- no de novo data available
Still missing
- No de novo testing data available for this variant
Sources
PS3 No functional assay data is available for this intronic variant. The PTEN VCEP specifies PS3 for RNA/mini-gene splicing assays (PS3_Strong) or phosphatase activity ≤ -1.11 per Mighell et al. 2018 (PS3_Moderate). The mmc2.xlsx (Mighell et al. saturation mutagenesis) is restricted to missense variants and does not apply to intronic variants. SpliceAI (max delta 0.01) is an in silico prediction tool, not a functional assay, and does not meet PS3 requirements. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01 — in silico only
- not a functional assay
- mmc2.xlsx is missense-only
- variant is not a missense substitution
Still missing
- No RNA or mini-gene splicing assay data available
Sources
spliceai ↗vcep_mmc2
PS4 No proband data or case-control studies are available for this variant. The variant is absent from ClinVar with zero submissions, and no published proband counts or specificity scores are available. Details ▾Hide ▴
Evidence considered
- Variant absent from ClinVar with zero submissions
- no proband or case-control data
Still missing
- No proband or phenotype data available
Sources
PM6 No de novo observations have been reported for this variant. The variant is absent from ClinVar and no literature reports assumed or confirmed de novo occurrence in a patient with PHTS and no family history. Details ▾Hide ▴
Evidence considered
- Variant absent from ClinVar
- no de novo reports available
Still missing
- No de novo testing data available
Sources
PP1 No co-segregation data is available for this variant. The PTEN VCEP requires at least 3-4 meioses for supporting-level PP1. No family studies or segregation analyses have been reported. Details ▾Hide ▴
Evidence considered
- No co-segregation or family studies available
Still missing
- No segregation or family data available
PP3 PP3 per PTEN VCEP requires multiple lines of computational evidence supporting a deleterious effect. For splicing variants, concordance of SpliceAI and VarSeak is required. SpliceAI predicts no splicing impact (max delta 0.01, all individual delta scores ≤0.01). No in silico tool predicts a deleterious effect on the gene product. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01 (DS_AG=0.0
- DS_AL=0.01
- DS_DG=0.01
- DS_DL=0.0) — no significant splice impact predicted
Still missing
- VarSeak data not available
Sources
BA1 The PTEN VCEP BA1 threshold is a filtering allele frequency >0.056% (0.00056) in gnomAD. This variant is absent from gnomAD v2.1 and v4.1 (AF = 0.00000%, 0/1,512,514 alleles). The allele frequency is well below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 0.00000% (0/1
- 512
- 514 alleles)
- BA1 threshold >0.056% not met
Sources
BS1 The PTEN VCEP BS1 threshold is an allele frequency from 0.0043% (strong) or 0.00043% (supporting) up to 0.056%. This variant is absent from gnomAD (AF = 0.00000%). The allele frequency is below even the supporting threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 0.00000%
- BS1 supporting threshold minimum 0.00043% not met
Sources
BS2 The PTEN VCEP BS2 requires observation in the homozygous state in a healthy or PHTS-unaffected individual. This variant is absent from gnomAD (0 homozygotes) and has no reported homozygous observations in any database. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 0 homozygotes
- no homozygous observations reported
Still missing
- No homozygous or clinical phenotype data available
Sources
BS3 The PTEN VCEP BS3_Strong requires an RNA, mini-gene, or other splicing assay demonstrating no splicing impact for intronic variants. The VCEP BS3_Supporting requires phosphatase activity >0 per Mighell et al. 2018, which applies only to missense variants. No functional assay data is available for this variant. SpliceAI (max delta 0.01) is an in silico tool and does not constitute a functional assay. Details ▾Hide ▴
Evidence considered
- No RNA/mini-gene splicing assay available
- mmc2.xlsx phosphatase assay applies to missense variants only
- SpliceAI delta 0.01 is in silico
- not functional assay
Still missing
- No functional splicing assay data available
Sources
spliceai ↗vcep_mmc2
BS4 No segregation data is available for this variant. The PTEN VCEP BS4 requires lack of segregation in affected members of one family (supporting) or two or more families (strong). No family studies have been reported. Details ▾Hide ▴
Evidence considered
- No segregation or family data available
Still missing
- No family or segregation data available
BP2 The PTEN VCEP BP2 requires observation in trans with a pathogenic or likely pathogenic PTEN variant, or at least three observations in cis/unknown phase with different pathogenic/likely pathogenic PTEN variants. No such observations have been reported for this variant. Details ▾Hide ▴
Evidence considered
- No trans or cis observations with pathogenic PTEN variants reported
Still missing
- No phase data available
BP4 The PTEN VCEP BP4 requires concordance of SpliceAI and VarSeak in silico models predicting no splicing impact for intronic variants. SpliceAI predicts no impact (max delta 0.01, within the benign 0-0.2 range). However, VarSeak data is not available, and the VCEP requires concordance of both tools. Without VarSeak, the criterion cannot be fully applied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01 — within benign range (0-0.2)
- VarSeak data unavailable — concordance required by VCEP not satisfied
Still missing
- VarSeak score not available
Sources
BP5 The PTEN VCEP BP5 requires the variant to be found in at least two cases with an alternate molecular basis for disease, where the other gene/disorder is highly penetrant and the patient's personal/family history shows no overlap with PTEN. No such cases have been reported for this variant. Details ▾Hide ▴
Evidence considered
- No cases with alternate molecular basis reported
Still missing
- No phenotype or alternate diagnosis data available
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is a deep intronic substitution at c.802-29 (29 bases upstream of exon 8), not a canonical ±1,2 splice site disruption. The PTEN VCEP PVS1 decision tree (PVS1_DecisionTree_PTEN.pdf) only covers nonsense, frameshift, canonical GT-AG splice site disruptions, and single/multi-exon deletions. Deep intronic variants are not within scope of the PTEN PVS1 framework. Details ▾Hide ▴
Evidence considered
- PTEN PVS1 decision tree: covers canonical GT-AG ±1
- 2 splice sites only
- c.802-29C>A is at position -29
- outside the canonical splice consensus
Sources
vcep_pvs1_decisiontree_pten
PS1 N/APS1 requires the same amino acid change as a previously established pathogenic variant regardless of nucleotide change, or a different variant at the same nucleotide position as a known pathogenic splicing variant. This is an intronic variant at c.802-29 with no known protein consequence (NP_000305.3:p.?). There is no amino acid change to compare and no established pathogenic variant at this nucleotide position. Details ▾Hide ▴
Evidence considered
- Intronic variant at c.802-29
- no protein consequence defined
PM1 N/APM1 per PTEN VCEP requires location in a catalytic motif at residues 90-94, 123-130, or 166-168 (NP_000305.3). This is an intronic variant at c.802-29 with no defined amino acid position. The variant does not alter any protein residue and SpliceAI predicts no splicing impact (max delta 0.01), so it does not disrupt any functional domain. Details ▾Hide ▴
Evidence considered
- Intronic variant at c.802-29
- no amino acid position in catalytic domain
- SpliceAI max delta 0.01 predicts no splicing impact
Sources
PM5 N/APM5 per PTEN VCEP requires a missense change at an amino acid residue where a different missense change has been determined to be pathogenic or likely pathogenic. This is an intronic variant with no amino acid change. The pm5_candidates.json confirms the variant class is not missense-like and is not eligible for classic same-residue PM5. Details ▾Hide ▴
Evidence considered
- Intronic variant c.802-29C>A
- not a missense variant
- no amino acid residue to compare
PP2 N/APP2 is restricted to missense variants in a gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. This variant is intronic (c.802-29C>A), not a missense variant. Details ▾Hide ▴
Evidence considered
- Intronic variant
- PP2 applies only to missense variants
PP4 VCEPPP4 is designated as Not Applicable by the ClinGen PTEN Expert Panel. Phenotype specificity has been incorporated into PS4 rule specifications. Details ▾Hide ▴
Evidence considered
- PTEN VCEP v3.2: PP4 Not Applicable — phenotype specificity incorporated into PS4
Sources
PP5 VCEPPP5 is designated as Not Applicable by the ClinGen PTEN Expert Panel. Additionally, this variant is absent from ClinVar entirely, so no expert panel pathogenic classification exists to cite. Details ▾Hide ▴
BP1 VCEPBP1 is designated as Not Applicable by the ClinGen PTEN Expert Panel. BP1 applies to truncating variants in genes where loss of function is not a known disease mechanism, which does not apply to PTEN. Details ▾Hide ▴
BP6 VCEPBP6 is designated as Not Applicable for this VCEP by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Additionally, this variant is absent from ClinVar, so no reputable source has reported it as benign. Details ▾Hide ▴
PS5 N/APS5 is not a standard ACMG/AMP 2015 criterion and is not defined in the ClinGen PTEN Expert Panel Specifications v3.2. This intronic variant has no protein-level comparator to assess. Details ▾Hide ▴
Evidence considered
- Not a standard ACMG criterion
- not present in PTEN VCEP v3.2
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.802-29C>A
- Protein (HGVS p.)
- NP_000305.3:p.?
- GRCh38
- chr10:87960865 C>A
- GRCh37
- chr10:89720622 C>A
Gene diagram
Every interpreted variant in PTEN, mapped onto the exon structure of NM_000314.8. Select a row to find it on the plot.
PTENNM_000314.8
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 PTEN
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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
0 / 1,512,514 alleles
AF 0 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0 · 0 / 1,512,514 alleles · 0 hom
No alternate alleles recorded in the displayed ancestry groups.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1512514 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/59236 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP7 SupportingThis is an intronic variant at c.802-29, which is beyond the -21 position from the exon 8 splice acceptor. SpliceAI predicts no impact to the splice consensus sequence and no creation of a new splice site (max delta 0.01, with individual delta scores: DS_AG=0.0, DS_AL=0.01, DS_DG=0.01, DS_DL=0.0). The PTEN VCEP BP7 applies at supporting level for intronic variants at or beyond +7/-21 where splicing prediction algorithms predict no impact. Details ▾Hide ▴
Evidence considered
- Intronic variant at c.802-29 (beyond -21 from exon 8 splice acceptor)
- SpliceAI max delta 0.01 (DS_AG=0.0
- DS_AL=0.01
- DS_DG=0.01
- DS_DL=0.0) — no splice impact predicted
Sources
PP3 PP3 per PTEN VCEP requires multiple lines of computational evidence supporting a deleterious effect. For splicing variants, concordance of SpliceAI and VarSeak is required. SpliceAI predicts no splicing impact (max delta 0.01, all individual delta scores ≤0.01). No in silico tool predicts a deleterious effect on the gene product. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01 (DS_AG=0.0
- DS_AL=0.01
- DS_DG=0.01
- DS_DL=0.0) — no significant splice impact predicted
Still missing
- VarSeak data not available
Sources
BP4 The PTEN VCEP BP4 requires concordance of SpliceAI and VarSeak in silico models predicting no splicing impact for intronic variants. SpliceAI predicts no impact (max delta 0.01, within the benign 0-0.2 range). However, VarSeak data is not available, and the VCEP requires concordance of both tools. Without VarSeak, the criterion cannot be fully applied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01 — within benign range (0-0.2)
- VarSeak data unavailable — concordance required by VCEP not satisfied
Still missing
- VarSeak score not available
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
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.
gnomAD v4.1
0 / 1,512,514 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC 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/135637575
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_000314.8%3Ac.802-29C%3EA
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89720622-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87960865-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/10-87960865-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.802-…
- OncoKB ↗www.oncokb.org/gene/PTEN/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PTEN+c.802-29C%3EA
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1512514 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/59236 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
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 = 0.01).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).