About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.890_899del, p.(Asp297AlafsTer7)
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.890_899del, predicted to result in p.(Asp297AlafsTer7) / p.(D297Afs*7). Under the PTEN-specific PVS1 decision tree, truncating variants with the stop/disruption at or 5' to p.D375 (c.1121) in the biologically relevant transcript NM_000314.8 meet PVS1; this variant is upstream of that threshold and PTEN loss of function is an established disease mechanism.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 and absent from gnomAD v4.1. The PTEN Expert Panel PM2 threshold is allele frequency below 0.00001 (0.001%), with subpopulation allowance below 0.00002 (0.002%) if multiple alleles are present; the observed frequency is therefore below threshold and supports PM2 at supporting strength.
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
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. 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.890_899del (p.(Asp297AlafsTer7), p.(D297Afs*7)) 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 Expert Panel PM2_Supporting threshold of 0.00001 (0.001%).
This deletion causes a frameshift with premature termination, and under the PTEN-specific PVS1 decision tree a stop/disruption at or 5' to p.D375 (c.1121) in NM_000314.8 supports PVS1.
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.02; however, computational missense or splice criteria are not the primary basis for interpreting this truncating deletion.
No criteria match.
Met · 2
PVS1 Very strongThis variant is a frameshift deletion in PTEN, NM_000314.8:c.890_899del, predicted to result in p.(Asp297AlafsTer7) / p.(D297Afs*7). Under the PTEN-specific PVS1 decision tree, truncating variants with the stop/disruption at or 5' to p.D375 (c.1121) in the biologically relevant transcript NM_000314.8 meet PVS1; this variant is upstream of that threshold and PTEN loss of function is an established disease mechanism. Details ▾Hide ▴
Rule
PTEN EP PVS1 decision tree: stop codon or disruption at or 5' to p.D375 (c.1121) in NM_000314.8 -> PVS1
Evidence considered
- Frameshift consequence p.(Asp297AlafsTer7) / p.(D297Afs*7)
- PTEN-specific PVS1 threshold at p.D375 (c.1121)
- PTEN loss of function supported as disease mechanism
Sources
PM2 SupportingThis variant is absent from gnomAD v2.1 and absent from gnomAD v4.1. The PTEN Expert Panel PM2 threshold is allele frequency below 0.00001 (0.001%), with subpopulation allowance below 0.00002 (0.002%) if multiple alleles are present; the observed frequency is therefore below threshold and supports PM2 at supporting strength. Details ▾Hide ▴
Rule
PTEN PM2_Supporting: absent or <0.00001, with subpopulation allowance <0.00002 if multiple alleles are present
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- PTEN PM2_Supporting threshold <0.00001
Sources
Not met · 3 · evaluated, threshold not reached
PM1 This variant affects residue 297, which is outside the PTEN Expert Panel catalytic motif residues 90-94, 123-130, and 166-168 defined for PM1. No statistically significant hotspot evidence was identified for this site. Details ▾Hide ▴
Rule
PTEN PM1 motifs: residues 90-94, 123-130, 166-168
Evidence considered
- PTEN PM1 catalytic motif boundaries
- No hotspot row identified for D297
Sources
BA1 This variant is absent from gnomAD v2.1 and absent from gnomAD v4.1, so it does not meet the PTEN BA1 stand-alone benign threshold of filtering allele frequency greater than 0.00056 (0.056%). Details ▾Hide ▴
Rule
PTEN BA1 threshold >0.00056
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BA1 threshold >0.00056
Sources
BS1 This variant is absent from gnomAD v2.1 and absent from gnomAD v4.1, so it does not meet the PTEN BS1 thresholds of 0.0000043 to 0.000043 for supporting evidence or 0.000043 to 0.00056 for strong evidence. Details ▾Hide ▴
Rule
PTEN BS1 thresholds: Supporting 0.0000043-0.000043; Strong 0.000043-0.00056
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BS1 thresholds from PTEN EP
Sources
Not assessed · 10 · no assessment recorded
PS2 No confirmed de novo occurrence with maternity and paternity established was identified for this variant, so PS2 is not assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar record with de novo information identified
Still missing
- Documented confirmed de novo case with phenotype information
Sources
PS3 No variant-specific functional study demonstrating a damaging effect was identified for this deletion. The PTEN saturation mutagenesis assay referenced by the PTEN Expert Panel applies to missense variants, not this frameshift deletion, and no RNA study showing abnormal splicing was identified. Details ▾Hide ▴
Evidence considered
- PTEN EP functional missense assay guidance
- No RNA/splicing assay identified
- SpliceAI max delta 0.02 does not indicate a strong splice signal
Still missing
- Variant-specific functional assay
- RNA or splicing assay if relevant
Sources
PS4 No affected-case series, specificity score, or case-control enrichment data were identified for this variant, so PS4 is not assessed. Details ▾Hide ▴
Evidence considered
- Absent from ClinVar
- No COSMIC result found
Still missing
- Affected-case counts with PTEN-specific phenotype scoring
- Case-control enrichment data
Sources
PM6 No presumed de novo occurrence was identified for this variant, so PM6 is not assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar record with presumed de novo information identified
Still missing
- Case-level inheritance information without full parental confirmation
Sources
PP1 No segregation data were identified for this variant, so PP1 is not assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar record with segregation information identified
Still missing
- Family segregation data with informative meioses
Sources
BS2 No observations of this variant in a healthy or PTEN-hamartoma-tumor-syndrome-unaffected homozygous individual were identified, so BS2 is not assessed. Details ▾Hide ▴
Evidence considered
- Variant absent from gnomAD v2.1 and gnomAD v4.1
Still missing
- Documented homozygous observations in unaffected individuals
Sources
BS3 No well-established study showing no damaging effect was identified for this deletion. The PTEN functional assay referenced by the Expert Panel is a missense assay, and no RNA study demonstrating normal splicing was identified. Details ▾Hide ▴
Evidence considered
- PTEN EP benign functional rule
- Missense assay not applicable to this frameshift
- SpliceAI max delta 0.02
Still missing
- Variant-specific functional study showing no damaging effect
- RNA study showing no splicing impact if relevant
Sources
BS4 No lack-of-segregation data were identified for this variant, so BS4 is not assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar record with family segregation information identified
Still missing
- Family data showing non-segregation in one or more families
Sources
BP2 No phase data were identified showing this variant in trans with a pathogenic PTEN variant or in cis/phase-unknown with multiple pathogenic PTEN variants, so BP2 is not assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar record with phase information identified
Still missing
- Phase information with other pathogenic PTEN variants
Sources
BP5 No evidence was identified that this variant was found in a case with an alternate highly penetrant molecular explanation and no overlap with PTEN-related disease, so BP5 is not assessed. Details ▾Hide ▴
Still missing
- Case-level alternate molecular diagnosis and phenotype comparison
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 is not applicable because this variant is a frameshift deletion, not an alternate nucleotide change producing the same amino acid substitution or the same predicted splice effect as a previously established pathogenic variant. Details ▾Hide ▴
Evidence considered
- Frameshift deletion rather than missense or equivalent splice variant
Sources
PM3 VCEPPM3 is not applicable in the PTEN Expert Panel framework. Details ▾Hide ▴
PM4 N/APM4 is not applicable because this variant is a frameshift deletion rather than an in-frame insertion/deletion or stop-loss variant. Details ▾Hide ▴
PM5 N/APM5 is not applicable because the PTEN framework uses classic same-residue missense PM5 logic, and this variant is a frameshift deletion rather than a missense change. Details ▾Hide ▴
Evidence considered
- PM5 mode is classic same-residue missense
- Variant class is not missense-like
Sources
cspec ↗pm5_candidates
PP2 N/APP2 is not applicable because this variant is not a missense change. Details ▾Hide ▴
PP3 N/APP3 is not applied because the PTEN computational rule is intended for missense variants with REVEL greater than 0.7 or splicing variants with concordant splice predictors, and this variant is a frameshift deletion. SpliceAI showed no significant splice impact with a maximum delta score of 0.02, but that does not substitute for the truncating consequence that already drives interpretation. Details ▾Hide ▴
Evidence considered
- Variant is not missense
- SpliceAI max delta score 0.02
- No REVEL or BayesDel because variant is not an SNV
Sources
PP4 VCEPPP4 is not applicable in the PTEN Expert Panel framework because phenotype specificity is incorporated into PS4. Details ▾Hide ▴
PP5 VCEPPP5 is not applicable in the PTEN Expert Panel framework. Details ▾Hide ▴
BP1 VCEPBP1 is not applicable in the PTEN Expert Panel framework. Details ▾Hide ▴
BP3 VCEPBP3 is not applicable in the PTEN Expert Panel framework. Details ▾Hide ▴
BP4 N/ABP4 is not applied because the PTEN computational benign rule is intended for missense variants with REVEL below 0.5 or synonymous/intronic splicing variants with concordant benign splice predictions. This variant is a frameshift deletion; SpliceAI showed a low maximum delta score of 0.02, but that does not convert a truncating variant into benign computational evidence. Details ▾Hide ▴
Evidence considered
- Variant is a frameshift deletion
- SpliceAI max delta 0.02
- No REVEL because variant is not an SNV
Still missing
- VarSeak result is not available for formal PTEN splicing BP4 assessment
Sources
BP6 VCEPBP6 is not applicable in the PTEN Expert Panel framework. Details ▾Hide ▴
BP7 N/ABP7 is not applicable because this variant is not a synonymous or qualifying deep intronic change. Details ▾Hide ▴
Evidence considered
- Frameshift coding deletion rather than synonymous/intronic variant
Sources
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.890_899del
- Protein (HGVS p.)
- NP_000305.3:p.(Asp297AlafsTer7)
- GRCh38
- chr10:87960981 GATCAAGAAAT>G
- GRCh37
- chr10:89720738 GATCAAGAAAT>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/APP3 is not applied because the PTEN computational rule is intended for missense variants with REVEL greater than 0.7 or splicing variants with concordant splice predictors, and this variant is a frameshift deletion. SpliceAI showed no significant splice impact with a maximum delta score of 0.02, but that does not substitute for the truncating consequence that already drives interpretation. Details ▾Hide ▴
Evidence considered
- Variant is not missense
- SpliceAI max delta score 0.02
- No REVEL or BayesDel because variant is not an SNV
Sources
BP4 N/ABP4 is not applied because the PTEN computational benign rule is intended for missense variants with REVEL below 0.5 or synonymous/intronic splicing variants with concordant benign splice predictions. This variant is a frameshift deletion; SpliceAI showed a low maximum delta score of 0.02, but that does not convert a truncating variant into benign computational evidence. Details ▾Hide ▴
Evidence considered
- Variant is a frameshift deletion
- SpliceAI max delta 0.02
- No REVEL because variant is not an SNV
Still missing
- VarSeak result is not available for formal PTEN splicing BP4 assessment
Sources
BP7 N/ABP7 is not applicable because this variant is not a synonymous or qualifying deep intronic change. Details ▾Hide ▴
Evidence considered
- Frameshift coding deletion rather than synonymous/intronic variant
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
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 0.020
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.890_899del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89720738-GATCAAGAAAT-G?dat…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87960981-GATCAAGAAAT-G?…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.890_…
- OncoKB ↗www.oncokb.org/gene/PTEN/D297Afs*7
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PTEN+c.890_899del
- 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 = 0.02).
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.