About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.449_456del, p.(Glu150GlyfsTer27)
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 deletion in PTEN, NM_000314.8:c.449_456del, predicted to cause p.(Glu150GlyfsTer27). It occurs in exon 5 of the biologically relevant transcript and introduces a premature termination codon well 5' of the PTEN-specific c.1121 (p.D375) threshold, which meets the PTEN Expert Panel PVS1 decision tree for full-strength PVS1.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 and gnomAD v4.1. Its observed population frequency is therefore below the PTEN Expert Panel PM2 threshold of 0.001% and supports PM2 at the supporting level.
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.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. 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 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
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
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 · 3 not met · 10 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.449_456del (p.Glu150GlyfsTer27) 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, placing it below the PTEN Expert Panel PM2 population threshold of 0.001%.
This deletion is predicted to cause a frameshift with premature protein truncation, and under the PTEN-specific PVS1 decision tree its position 5' of c.1121 (p.D375) supports loss of function; SpliceAI does not predict an additional splice effect (maximum delta score 0.01).
No criteria match.
Met · 2
PVS1 Very strongThis variant is a frameshift deletion in PTEN, NM_000314.8:c.449_456del, predicted to cause p.(Glu150GlyfsTer27). It occurs in exon 5 of the biologically relevant transcript and introduces a premature termination codon well 5' of the PTEN-specific c.1121 (p.D375) threshold, which meets the PTEN Expert Panel PVS1 decision tree for full-strength PVS1. Details ▾Hide ▴
Rule
PTEN VCEP PVS1 decision tree: truncating variant at or 5' to c.1121 (p.D375) in NM_000314.8 qualifies for PVS1.
Evidence considered
- Frameshift consequence p.(Glu150GlyfsTer27)
- Variant maps to exon 5
- PTEN-specific PVS1 threshold at c.1121/p.D375
Sources
PM2 SupportingThis variant is absent from gnomAD v2.1 and gnomAD v4.1. Its observed population frequency is therefore below the PTEN Expert Panel PM2 threshold of 0.001% and supports PM2 at the supporting level. Details ▾Hide ▴
Rule
PTEN VCEP PM2 specification: absent or <0.001% in gnomAD supports PM2_Supporting.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- PM2 threshold <0.001%
Sources
Not met · 3 · evaluated, threshold not reached
PM1 This variant affects codon 150. The PTEN Expert Panel PM1 rule is defined for catalytic motif residues 90-94, 123-130, and 166-168, and no hotspot evidence was identified at residue 150, so PM1 is not met. Details ▾Hide ▴
Rule
PTEN VCEP PM1 specification.
Evidence considered
- Affected residue is E150
- PTEN PM1 motifs are 90-94
- 123-130
- and 166-168
- No hotspot row identified
Sources
BA1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, so its population frequency is below the PTEN BA1 threshold of 0.056% and BA1 is not met. Details ▾Hide ▴
Rule
PTEN VCEP BA1 specification.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BA1 threshold >0.056%
Sources
BS1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, so its population frequency is below the PTEN BS1 thresholds of 0.00043% for supporting and 0.0043% for strong evidence. BS1 is not met. Details ▾Hide ▴
Rule
PTEN VCEP BS1 specification.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BS1 supporting threshold 0.00043%
- BS1 strong threshold 0.0043%
Sources
Not assessed · 10 · no assessment recorded
PS2 No confirmed de novo observation with documented maternity and paternity testing was identified for this variant, so PS2 is not met from the available evidence. Details ▾Hide ▴
PS3 No variant-specific functional assay or RNA study was identified for this frameshift deletion. The available PTEN functional assay resource in Mighell et al. is a missense assay and does not adjudicate this variant. Details ▾Hide ▴
Rule
PTEN VCEP PS3 specification.
Evidence considered
- PTEN missense phosphatase assay resource is not applicable to this frameshift variant
- OncoKB provided literature leads but not a directly adjudicable variant-specific functional result
Still missing
- Variant-specific RNA or functional study
Sources
PS4 No case series, prevalence comparison, or PTEN-specific proband scoring data were identified for this exact variant, so PS4 cannot be applied from the available evidence. Details ▾Hide ▴
Rule
PTEN VCEP PS4 specification.
Evidence considered
- Variant absent from ClinVar in this review set
- Variant absent from gnomAD but no affected-case enrichment data identified
Still missing
- Unrelated affected proband counts or case-control enrichment data
Sources
PM6 No assumed de novo observation without parental confirmation was identified for this variant, so PM6 cannot be applied from the available evidence. Details ▾Hide ▴
PP1 No segregation data were identified for this variant, so PP1 cannot be applied. Details ▾Hide ▴
Rule
PTEN VCEP PP1 specification.
Evidence considered
- No segregation evidence identified
Still missing
- Pedigree or informative meiosis data showing segregation with disease
Sources
BS2 No observations of this variant in healthy or PTEN hamartoma tumor syndrome-unaffected homozygous individuals were identified, so BS2 cannot be applied. Details ▾Hide ▴
Rule
PTEN VCEP BS2 specification.
Evidence considered
- Variant absent from gnomAD
- No unaffected homozygous observations identified
Still missing
- Documented unaffected homozygous observations
Sources
BS3 No well-established functional study showing no damaging effect was identified for this variant. The available PTEN missense phosphatase assay resource does not adjudicate this frameshift deletion. Details ▾Hide ▴
Rule
PTEN VCEP BS3 specification.
Evidence considered
- Missense assay resource not applicable to this frameshift variant
Still missing
- Variant-specific functional evidence demonstrating no damaging effect
Sources
cspec ↗vcep_mmc2
BS4 No lack-of-segregation evidence was identified for this variant, so BS4 cannot be applied. Details ▾Hide ▴
Rule
PTEN VCEP BS4 specification.
Evidence considered
- No nonsegregation evidence identified
Still missing
- Family data showing lack of segregation in one or more families
Sources
BP2 No phase-resolved co-occurrence with another pathogenic or likely pathogenic PTEN variant was identified, so BP2 cannot be applied. Details ▾Hide ▴
Rule
PTEN VCEP BP2 specification.
Evidence considered
- No co-occurrence evidence identified
Still missing
- Documented in trans co-occurrence or repeated cis/phase-unknown observations with a pathogenic PTEN variant
Sources
BP5 No evidence was identified that this variant was found in an individual with a distinct alternate molecular diagnosis and non-overlapping clinical features, so BP5 cannot be applied. Details ▾Hide ▴
Rule
PTEN VCEP BP5 specification.
Evidence considered
- No alternate molecular diagnosis evidence identified
Still missing
- Documented alternate molecular diagnosis with non-overlapping phenotype
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 applies to the same amino acid substitution as a previously established pathogenic variant or to certain equivalent splice effects. This variant is a frameshift deletion, so PS1 is not applicable. Details ▾Hide ▴
Rule
PTEN VCEP PS1 specification.
Evidence considered
- Variant consequence is frameshift
- not a single amino acid substitution
Sources
PM3 VCEPPM3 is designated not applicable in the PTEN Expert Panel specifications. Details ▾Hide ▴
VCEP rule
PTEN VCEP PM3 applicability.
Evidence considered
- PTEN VCEP marks PM3 not applicable
Sources
PM4 N/APM4 applies to in-frame insertions or deletions and stop-loss variants. This variant is a frameshift deletion, so PM4 is not applicable. Details ▾Hide ▴
Rule
PTEN VCEP PM4 specification.
Evidence considered
- Variant class is frameshift
Sources
cspec ↗pvs1_variant_assessment
PM5 N/APTEN uses classic same-residue missense PM5 logic. This variant is a frameshift deletion rather than a missense variant, so PM5 is not applicable. Details ▾Hide ▴
Rule
PTEN VCEP PM5 specification.
Evidence considered
- PM5 framework is classic same-residue missense
- Variant class is not missense-like
Sources
cspec ↗pm5_candidates
PP2 N/APP2 is a missense criterion. This variant is a frameshift deletion, so PP2 is not applicable. Details ▾Hide ▴
PP3 N/APTEN PP3 is specified for missense variants with REVEL >0.7 or for splicing variants with concordant splice prediction evidence. This variant is a frameshift deletion; REVEL and BayesDel were not applicable, and SpliceAI showed no significant splice effect with a maximum delta score of 0.01, so PP3 is not used. Details ▾Hide ▴
Rule
PTEN VCEP PP3 specification.
Evidence considered
- REVEL not applicable for non-SNV
- BayesDel not applicable for non-SNV
- SpliceAI max delta score 0.01
Sources
PP4 VCEPPP4 is designated not applicable in the PTEN Expert Panel specifications because phenotype specificity is incorporated into PS4. Details ▾Hide ▴
VCEP rule
PTEN VCEP PP4 applicability.
Evidence considered
- PTEN VCEP marks PP4 not applicable
Sources
PP5 VCEPPP5 is designated not applicable in the PTEN Expert Panel specifications. Details ▾Hide ▴
VCEP rule
PTEN VCEP PP5 applicability.
Evidence considered
- PTEN VCEP marks PP5 not applicable
Sources
BP1 VCEPBP1 is designated not applicable in the PTEN Expert Panel specifications. Details ▾Hide ▴
VCEP rule
PTEN VCEP BP1 applicability.
Evidence considered
- PTEN VCEP marks BP1 not applicable
Sources
BP3 VCEPBP3 is designated not applicable in the PTEN Expert Panel specifications. Details ▾Hide ▴
VCEP rule
PTEN VCEP BP3 applicability.
Evidence considered
- PTEN VCEP marks BP3 not applicable
Sources
BP4 N/APTEN BP4 is specified for synonymous or intronic variants with benign splice predictions or for missense variants with REVEL <0.5. This variant is a frameshift deletion; although SpliceAI predicts no significant splice effect with a maximum delta score of 0.01, the BP4 rule is not applicable to this variant class. Details ▾Hide ▴
Rule
PTEN VCEP BP4 specification.
Evidence considered
- Variant is frameshift
- not synonymous
- intronic
- or missense
- SpliceAI max delta score 0.01
Sources
BP6 VCEPBP6 is designated not applicable in the PTEN Expert Panel specifications. Details ▾Hide ▴
VCEP rule
PTEN VCEP BP6 applicability.
Evidence considered
- PTEN VCEP marks BP6 not applicable
Sources
BP7 N/ABP7 applies to synonymous or qualifying deep intronic variants with no predicted splice impact. This variant is a coding frameshift deletion, so BP7 is not applicable. Details ▾Hide ▴
Rule
PTEN VCEP BP7 specification.
Evidence considered
- Variant is not synonymous or qualifying intronic
- SpliceAI max delta score 0.01
Sources
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.449_456del
- Protein (HGVS p.)
- NP_000305.3:p.(Glu150GlyfsTer27)
- GRCh38
- chr10:87933207 GAGGCCCTA>G
- GRCh37
- chr10:89692964 GAGGCCCTA>G
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.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/APTEN PP3 is specified for missense variants with REVEL >0.7 or for splicing variants with concordant splice prediction evidence. This variant is a frameshift deletion; REVEL and BayesDel were not applicable, and SpliceAI showed no significant splice effect with a maximum delta score of 0.01, so PP3 is not used. Details ▾Hide ▴
Rule
PTEN VCEP PP3 specification.
Evidence considered
- REVEL not applicable for non-SNV
- BayesDel not applicable for non-SNV
- SpliceAI max delta score 0.01
Sources
BP4 N/APTEN BP4 is specified for synonymous or intronic variants with benign splice predictions or for missense variants with REVEL <0.5. This variant is a frameshift deletion; although SpliceAI predicts no significant splice effect with a maximum delta score of 0.01, the BP4 rule is not applicable to this variant class. Details ▾Hide ▴
Rule
PTEN VCEP BP4 specification.
Evidence considered
- Variant is frameshift
- not synonymous
- intronic
- or missense
- SpliceAI max delta score 0.01
Sources
BP7 N/ABP7 applies to synonymous or qualifying deep intronic variants with no predicted splice impact. This variant is a coding frameshift deletion, so BP7 is not applicable. Details ▾Hide ▴
Rule
PTEN VCEP BP7 specification.
Evidence considered
- Variant is not synonymous or qualifying intronic
- SpliceAI max delta score 0.01
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
2 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 11237521 ↗PTEN: life as a tumor suppressor.No paper-specific finding is recorded.
-
PMID 17218262 ↗Essential role for nuclear PTEN in maintaining chromosomal integrity.No paper-specific finding is recorded.
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
Recorded maximum delta 0.010
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.449_456del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89692964-GAGGCCCTA-G?datas…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87933207-GAGGCCCTA-G?da…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.449_…
- OncoKB ↗www.oncokb.org/gene/PTEN/E150Gfs*27
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PTEN+c.449_456del
- 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 = 0.01).
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.