About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.570_571delinsT, p.(Val191TrpfsTer8)
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
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 v3.2.0. 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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PVS1Very strong
PVS1 · very strong
This variant is a frameshift, NM_000314.8:c.570_571delinsT, predicted to result in p.(Val191TrpfsTer8) [p.(V191Wfs*8)] with a premature stop codon well 5' to the PTEN VCEP p.D375 (c.1121) threshold. PTEN loss of function is an established disease mechanism, and the PTEN-specific PVS1 decision tree supports full-strength PVS1 for truncating variants in this region of the biologically relevant transcript.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 and gnomAD v4.1. Under the PTEN VCEP specification, PM2_Supporting is met when the allele frequency is <0.001% and, if multiple alleles are present in any subpopulation, that subpopulation frequency is <0.002%; this variant is below those thresholds.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework: matched Rule20 (1 Pathogenic.Very Strong + 1 Pathogenic.Supporting) with applied criteria: PVS1 very strong, PM2 supporting; maps to Likely Pathogenic.
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PTEN VCEP v3.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 4 not met · 9 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
The PTEN c.570_571delinsT (p.Val191TrpfsTer8; p.V191Wfs*8) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.
This variant is absent from gnomAD v2.1 and gnomAD v4.1, which is below the PTEN VCEP PM2_Supporting population threshold of 0.001%.
This frameshift is predicted to introduce a premature stop codon after 8 altered amino acids at codon 191, and the PTEN VCEP PVS1 decision tree supports PVS1 for truncating variants at or 5' to p.D375 in the biologically relevant transcript NM_000314.8.
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.06.
No criteria match.
Met · 2
PVS1 Very strongThis variant is a frameshift, NM_000314.8:c.570_571delinsT, predicted to result in p.(Val191TrpfsTer8) [p.(V191Wfs*8)] with a premature stop codon well 5' to the PTEN VCEP p.D375 (c.1121) threshold. PTEN loss of function is an established disease mechanism, and the PTEN-specific PVS1 decision tree supports full-strength PVS1 for truncating variants in this region of the biologically relevant transcript. Details ▾Hide ▴
Rule
PTEN VCEP PVS1 decision tree: truncating variants at or 5' to p.D375 in NM_000314.8 are assigned PVS1.
Evidence considered
- Frameshift consequence p.(Val191TrpfsTer8) / p.(V191Wfs*8)
- PTEN VCEP PVS1 decision tree uses p.D375 (c.1121) threshold
- PTEN loss of function is an established disease mechanism
Sources
PM2 SupportingThis variant is absent from gnomAD v2.1 and gnomAD v4.1. Under the PTEN VCEP specification, PM2_Supporting is met when the allele frequency is <0.001% and, if multiple alleles are present in any subpopulation, that subpopulation frequency is <0.002%; this variant is below those thresholds. Details ▾Hide ▴
Rule
PM2_Supporting for variants absent or below 0.001% allele frequency, with subpopulation constraint <0.002% if multiple alleles are present.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- PTEN PM2 threshold <0.001%
Sources
Not met · 4 · evaluated, threshold not reached
PM1 This variant affects codon 191, which is outside the PTEN catalytic motif residues defined for PM1 (90-94, 123-130, and 166-168). Available evidence does not support location in a PTEN mutational hotspot or critical domain specified for PM1. Details ▾Hide ▴
Rule
Located in a mutational hot spot and/or critical and well-established functional domain; PTEN catalytic motifs 90-94, 123-130, 166-168.
Evidence considered
- Protein position 191
- PTEN PM1 catalytic motifs: 90-94
- 123-130
- 166-168
- No hotspot evidence identified
Sources
BA1 This variant is absent from gnomAD and does not meet the PTEN BA1 population threshold of >0.056% allele frequency. Details ▾Hide ▴
Rule
gnomAD filtering allele frequency >0.056%.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BA1 threshold >0.056%
Sources
BS1 This variant is absent from gnomAD and does not meet the PTEN BS1 thresholds of 0.00043%-0.0043% for supporting evidence or 0.0043%-0.056% for strong evidence. Details ▾Hide ▴
Rule
BS1_Supporting at 0.00043%-0.0043%; BS1_Strong at 0.0043%-0.056%.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BS1 supporting and strong thresholds not reached
Sources
BS2 No homozygous observation in a healthy or PTEN hamartoma tumor syndrome-unaffected individual was identified, so BS2 is not met. Details ▾Hide ▴
Rule
Observed in the homozygous state in a healthy or PHTS-unaffected individual.
Evidence considered
- Variant absent from gnomAD
Sources
Not assessed · 9 · no assessment recorded
PS2 No confirmed de novo observation with maternity and paternity confirmed was identified for this variant, so PS2 cannot be applied from the available evidence. Details ▾Hide ▴
Rule
De novo occurrence in a patient with the disease and no family history.
Evidence considered
- No ClinVar record or case-level de novo data identified
Still missing
- Confirmed de novo case data with parental testing
- Phenotype details showing a PTEN-related presentation
Sources
PS3 No variant-specific functional assay showing a damaging effect was identified for this frameshift variant. The PTEN VCEP supplementary functional assay resource is directed to missense variants, and no RNA or other direct assay evidence was available for this variant. Details ▾Hide ▴
Rule
Apply for well-established functional studies supportive of a damaging effect; PTEN missense phosphatase activity <= -1.11 qualifies for PS3_Moderate.
Evidence considered
- PTEN VCEP missense functional assay resource applies to missense variants
- No variant-specific RNA or other functional assay identified
Still missing
- Variant-specific functional study
- RNA or splicing assay if clinically relevant
Sources
PS4 No affected proband count, specificity score, or case-control enrichment data were identified for this variant, so PS4 cannot be applied. Details ▾Hide ▴
Rule
Apply based on affected proband specificity score or significant enrichment in affected individuals versus controls.
Evidence considered
- Variant absent from ClinVar
- Variant not reported in COSMIC
Still missing
- Independent affected proband observations
- Specificity score or case-control enrichment data
Sources
PM6 No assumed or confirmed de novo observation was identified for this variant, so PM6 cannot be applied from the available evidence. Details ▾Hide ▴
Rule
Apply for assumed or multiple de novo observations according to PTEN VCEP strength specifications.
Evidence considered
- No ClinVar record or case-level de novo data identified
Still missing
- Assumed or confirmed de novo case data
- Phenotype details for any reported case
Sources
PP1 No segregation data were identified for this variant, so PP1 cannot be applied. Details ▾Hide ▴
Rule
Co-segregation with disease in multiple affected family members, with strength based on meiosis count.
Evidence considered
- No family segregation evidence identified
Still missing
- Family segregation data
- Informative meiosis counts
Sources
BS3 No variant-specific functional study showing no damaging effect was identified. The PTEN VCEP missense functional assay resource does not directly address this frameshift variant. Details ▾Hide ▴
Rule
Apply for well-established functional studies showing no damaging effect; PTEN missense phosphatase activity >0 qualifies for BS3_Supporting.
Evidence considered
- PTEN missense functional assay resource not directly applicable to this frameshift
Still missing
- Variant-specific benign functional evidence
Sources
cspec ↗vcep_mmc2
BS4 No nonsegregation data were identified for this variant, so BS4 cannot be applied. Details ▾Hide ▴
Rule
Lack of segregation in affected members of one or more families.
Evidence considered
- No family nonsegregation evidence identified
Still missing
- Family nonsegregation data
- Clinical context to interpret variable expression
Sources
BP2 No phase data were identified showing this variant in trans with a pathogenic PTEN variant or repeated cis/phase-unknown observations with different pathogenic PTEN variants, so BP2 cannot be applied. Details ▾Hide ▴
Rule
Observed in trans with a pathogenic/likely pathogenic PTEN variant or at least three cis/phase-unknown observations with different pathogenic variants.
Evidence considered
- No phase or compound observation data identified
Still missing
- Phase data with another pathogenic PTEN variant
Sources
BP5 No alternate highly penetrant molecular explanation with non-overlapping clinical features was identified, so BP5 cannot be applied. Details ▾Hide ▴
Rule
Variant found in a case with an alternate molecular basis for disease and no overlap with PTEN-related disease.
Evidence considered
- No alternate molecular basis data identified
Still missing
- Independent alternate molecular diagnosis with non-overlapping phenotype
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/AThis criterion is not applicable because the variant is a frameshift rather than a missense change or a nucleotide change being evaluated against a known pathogenic splicing variant at the same position. Details ▾Hide ▴
PM3 N/AThis criterion is not applicable in the PTEN VCEP framework. Details ▾Hide ▴
PM4 N/AThis criterion is not applicable because the variant is a frameshift rather than an in-frame insertion/deletion or stop-loss variant. Details ▾Hide ▴
Evidence considered
- Variant class: frameshift
- PTEN PM4 applies to in-frame insertions/deletions and stop-loss variants
Sources
cspec ↗pvs1_variant_assessment
PM5 N/AThis criterion is not applicable because the PTEN framework uses classic same-residue missense PM5 logic, and this variant is not missense. Details ▾Hide ▴
Evidence considered
- PM5 mode: classic same-residue missense
- Variant class is not missense-like
Sources
cspec ↗pm5_candidates
PP2 N/AThis criterion is not applicable because the variant is a frameshift rather than a missense variant. Details ▾Hide ▴
Evidence considered
- Variant class: frameshift
- PP2 is a missense criterion
Sources
cspec ↗pvs1_variant_assessment
PP3 N/AThis criterion is not applicable because the PTEN PP3 computational rule is intended for missense REVEL interpretation or concordant splicing prediction for splice-relevant variants. This frameshift variant has no REVEL or BayesDel score, and SpliceAI shows no significant splice impact (max delta score 0.06). Details ▾Hide ▴
Evidence considered
- No REVEL score
- No BayesDel score
- SpliceAI max delta score 0.06
Sources
PP4 N/AThis criterion is not applicable in the PTEN VCEP framework because phenotype specificity is incorporated into PS4 specifications. Details ▾Hide ▴
PP5 N/AThis criterion is not applicable in the PTEN VCEP framework. Details ▾Hide ▴
BP1 N/AThis criterion is not applicable in the PTEN VCEP framework. Details ▾Hide ▴
BP3 N/AThis criterion is not applicable in the PTEN VCEP framework. Details ▾Hide ▴
BP4 N/AThis criterion is not applicable because the PTEN BP4 computational rule is intended for synonymous or intronic variants with benign splicing predictions or missense variants with REVEL <0.5. This variant is a frameshift, and while SpliceAI predicts no significant splice impact (max delta score 0.06), that does not establish BP4 for this variant type. Details ▾Hide ▴
Evidence considered
- Variant class: frameshift
- SpliceAI max delta score 0.06
- No REVEL score because variant is not an SNV missense change
Sources
BP6 N/AThis criterion is not applicable in the PTEN VCEP framework. Details ▾Hide ▴
BP7 N/AThis criterion is not applicable because the variant is neither synonymous nor intronic at or beyond the BP7 distance thresholds. Details ▾Hide ▴
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.570_571delinsT
- Protein (HGVS p.)
- NP_000305.3:p.(Val191TrpfsTer8)
- GRCh38
- chr10:87952195 AG>T
- GRCh37
- chr10:89711952 AG>T
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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/AThis criterion is not applicable because the PTEN PP3 computational rule is intended for missense REVEL interpretation or concordant splicing prediction for splice-relevant variants. This frameshift variant has no REVEL or BayesDel score, and SpliceAI shows no significant splice impact (max delta score 0.06). Details ▾Hide ▴
Evidence considered
- No REVEL score
- No BayesDel score
- SpliceAI max delta score 0.06
Sources
BP4 N/AThis criterion is not applicable because the PTEN BP4 computational rule is intended for synonymous or intronic variants with benign splicing predictions or missense variants with REVEL <0.5. This variant is a frameshift, and while SpliceAI predicts no significant splice impact (max delta score 0.06), that does not establish BP4 for this variant type. Details ▾Hide ▴
Evidence considered
- Variant class: frameshift
- SpliceAI max delta score 0.06
- No REVEL score because variant is not an SNV missense change
Sources
BP7 N/AThis criterion is not applicable because the variant is neither synonymous nor intronic at or beyond the BP7 distance thresholds. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).
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
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
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/135637575
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_000314.8%3Ac.570_571delinsT
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89711952-AG-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87952195-AG-T?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.570_…
- OncoKB ↗www.oncokb.org/gene/PTEN/V191Wfs*8
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PTEN+c.570_571delinsT
- 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 v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.