About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.548del, p.(Lys183ArgfsTer16)
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
NM_000314.8:c.548del is a PTEN frameshift variant predicted to result in p.(Lys183ArgfsTer16) / p.(K183Rfs*16). Under the PTEN Expert Panel PVS1 decision tree, truncating variants at or 5' to p.D375 (c.1121) in transcript NM_000314.8 meet full-strength PVS1; c.548 is upstream of this threshold and PTEN loss of function is an established disease mechanism.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 and gnomAD v4.1. The observed allele frequency is 0, which is below the PTEN Expert Panel PM2 threshold of <0.00001 (0.001%) overall and below the subpopulation requirement of <0.00002 (0.002%), supporting 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.
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 classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
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 NM_000314.8:c.548del (NP_000305.3:p.(Lys183ArgfsTer16), p.(K183Rfs*16)) variant has been observed in somatic cancer databases once in COSMIC and has been reported in ClinVar as Pathogenic by a clinical laboratory.
This variant is absent from gnomAD v2.1 and gnomAD v4.1, with an observed allele frequency of 0, which is below the PTEN Expert Panel PM2 threshold of <0.00001 (0.001%).
This variant is a frameshift predicted to create a premature termination codon, and because c.548 is upstream of the PTEN Expert Panel p.D375 (c.1121) truncation threshold in transcript NM_000314.8, the finding is consistent with full-strength PVS1.
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.03.
No criteria match.
Met · 2
PVS1 Very strongNM_000314.8:c.548del is a PTEN frameshift variant predicted to result in p.(Lys183ArgfsTer16) / p.(K183Rfs*16). Under the PTEN Expert Panel PVS1 decision tree, truncating variants at or 5' to p.D375 (c.1121) in transcript NM_000314.8 meet full-strength PVS1; c.548 is upstream of this threshold and PTEN loss of function is an established disease mechanism. Details ▾Hide ▴
Rule
PTEN Expert Panel PVS1 decision tree: null variants at or 5' to p.D375 (c.1121) in NM_000314.8 are assigned PVS1.
Evidence considered
- Variant type is frameshift
- Protein consequence is p.(Lys183ArgfsTer16) / p.(K183Rfs*16)
- PTEN-specific PVS1 threshold is p.D375 (c.1121)
- PTEN loss of function is an established disease mechanism
Sources
PM2 SupportingThis variant is absent from gnomAD v2.1 and gnomAD v4.1. The observed allele frequency is 0, which is below the PTEN Expert Panel PM2 threshold of <0.00001 (0.001%) overall and below the subpopulation requirement of <0.00002 (0.002%), supporting PM2 at the Supporting level. Details ▾Hide ▴
Rule
PM2_Supporting for PTEN: absent or below <0.00001 overall, with any subpopulation <0.00002.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- PTEN PM2 threshold is <0.00001 overall and <0.00002 within any subpopulation
Sources
Not met · 4 · evaluated, threshold not reached
PM1 The protein change begins at Lys183, which is outside the PTEN catalytic motif residues defined for PM1 (90-94, 123-130, and 166-168). Cancer Hotspots also did not identify this site as a statistically significant hotspot, so PM1 is not met. Details ▾Hide ▴
Rule
PM1 applies to PTEN catalytic motif residues 90-94, 123-130, and 166-168.
Evidence considered
- Affected residue is Lys183
- PTEN PM1 catalytic motifs are residues 90-94
- 123-130
- and 166-168
- Cancer Hotspots did not identify a significant hotspot at this site
Sources
BA1 This variant is absent from gnomAD v2.1 and gnomAD v4.1. The observed allele frequency is 0, which is below the PTEN BA1 threshold of >0.00056 (0.056%), so BA1 is not met. Details ▾Hide ▴
Rule
BA1 applies when the filtering allele frequency is >0.00056.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- PTEN BA1 threshold is >0.00056
Sources
BS1 This variant is absent from gnomAD v2.1 and gnomAD v4.1. The observed allele frequency is 0, which is below the PTEN BS1 thresholds of 0.0000043-0.000043 for Supporting and 0.000043-0.00056 for Strong, so BS1 is not met. Details ▾Hide ▴
Rule
BS1 applies when allele frequency is within the PTEN benign frequency range.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- PTEN BS1 thresholds are 0.0000043-0.000043 and 0.000043-0.00056
Sources
BS2 This variant is absent from gnomAD v2.1 and gnomAD v4.1, and no homozygous observations in healthy or PTEN hamartoma tumor syndrome-unaffected individuals were identified. BS2 is not met. Details ▾Hide ▴
Rule
BS2 requires homozygous observations in healthy or PTEN hamartoma tumor syndrome-unaffected individuals.
Evidence considered
- No population observations were identified
- No homozygous unaffected observations were identified
Sources
Not assessed · 9 · no assessment recorded
PS2 No confirmed de novo observation with maternity and paternity established was identified for this variant. PS2 cannot be applied without documented de novo evidence in an affected individual with no family history. Details ▾Hide ▴
Rule
PS2 requires a confirmed de novo occurrence in an affected individual with no family history.
Evidence considered
- No confirmed de novo evidence was identified in the reviewed sources
Still missing
- No confirmed de novo case was identified
Sources
PS3 No variant-specific functional study meeting PTEN Expert Panel PS3 requirements was identified for this frameshift variant. The PTEN saturation mutagenesis functional dataset referenced for PS3 applies to missense variants and does not provide applicable evidence for this deletion. Details ▾Hide ▴
Rule
PS3 requires well-established functional evidence supportive of a damaging effect.
Evidence considered
- PTEN functional dataset in mmc2 is curated for missense variants
- No additional qualifying functional assay was identified for c.548del
Still missing
- No variant-specific phosphatase
- cellular
- animal
- RNA
- or splicing assay was identified for this variant
Sources
cspec ↗vcep_m_m_c_2
PS4 This variant has been reported in ClinVar as Pathogenic and has one somatic observation in COSMIC, but no case-count or case-control data were identified that establish the PTEN-specific phenotype specificity score required for PS4. Details ▾Hide ▴
Rule
PS4 requires PTEN-specific phenotype specificity scoring or significant enrichment in affected individuals versus controls.
Evidence considered
- ClinVar reports one pathogenic clinical laboratory submission
- COSMIC reports one somatic observation
- No PTEN-specific PS4 scoring evidence was identified
Still missing
- No phenotype-specific proband count or specificity score was identified
- No case-control enrichment data were identified
Sources
PM6 No assumed de novo observation without parental confirmation was identified for this variant. PM6 cannot be applied without documented de novo evidence in an affected individual. Details ▾Hide ▴
Rule
PM6 requires documented assumed de novo occurrence in an affected individual.
Evidence considered
- No presumed de novo evidence was identified in the reviewed sources
Still missing
- No presumed de novo case was identified
Sources
PP1 No segregation data were identified for this variant, so PP1 cannot be applied. Details ▾Hide ▴
Rule
PP1 requires co-segregation with disease in affected family members.
Evidence considered
- No family segregation evidence was identified
Still missing
- No informative segregation data were identified
Sources
BS3 No functional study showing normal PTEN function was identified for this frameshift variant. The PTEN saturation mutagenesis dataset referenced for BS3 applies to missense variants and does not provide benign functional evidence for this deletion. Details ▾Hide ▴
Rule
BS3 requires well-established functional evidence showing no damaging effect.
Evidence considered
- PTEN functional dataset in mmc2 is curated for missense variants
- No evidence showing preserved function was identified for c.548del
Still missing
- No variant-specific benign functional assay was identified
Sources
cspec ↗vcep_m_m_c_2
BS4 No lack-of-segregation data were identified for this variant, so BS4 cannot be applied. Details ▾Hide ▴
Rule
BS4 requires documented lack of segregation in one or more affected families.
Evidence considered
- No family non-segregation evidence was identified
Still missing
- No informative non-segregation data were identified
Sources
BP2 No phase data were identified showing this variant in trans with a pathogenic PTEN variant or repeatedly in cis/phase unknown with other pathogenic PTEN variants. BP2 cannot be applied. Details ▾Hide ▴
Rule
BP2 requires trans with a pathogenic PTEN variant or at least three cis/phase-unknown observations with different pathogenic PTEN variants.
Evidence considered
- No trans or repeated cis observations were identified
Still missing
- No phase data with another pathogenic PTEN variant were identified
Sources
BP5 No evidence was identified that this variant occurred in a case with an alternate highly penetrant molecular explanation for the phenotype and no clinical overlap with PTEN-related disease. BP5 cannot be applied. Details ▾Hide ▴
Rule
BP5 requires an alternate highly penetrant molecular explanation and a non-overlapping phenotype.
Evidence considered
- No qualifying alternate molecular basis for disease was identified
Still missing
- No alternate molecular diagnosis meeting PTEN BP5 requirements was identified
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/AThis variant is a frameshift deletion and does not represent an alternate nucleotide change producing the same amino acid substitution as a previously established pathogenic variant. PS1 is not applicable. Details ▾Hide ▴
Rule
PS1 applies to the same amino acid change as a previously established pathogenic variant or an equivalent splicing effect at the same nucleotide position.
Evidence considered
- Variant consequence is frameshift
Sources
PM3 N/AThe PTEN Expert Panel specification designates PM3 as not applicable. Details ▾Hide ▴
Rule
PTEN Expert Panel: PM3 not applicable.
Evidence considered
- PTEN Expert Panel specification lists PM3 as not applicable
Sources
PM4 N/AThis variant is a frameshift deletion, not an in-frame insertion/deletion or stop-loss variant. PTEN Expert Panel PM4 is therefore not applicable. Details ▾Hide ▴
Rule
PM4 applies to in-frame insertions/deletions and stop-loss variants.
Evidence considered
- Variant consequence is frameshift
Sources
PM5 N/APM5 is a missense-specific criterion for a different pathogenic missense change at the same residue. This variant is a frameshift deletion, so PM5 is not applicable. Details ▾Hide ▴
Rule
PM5 applies to missense changes at a residue with a different established pathogenic missense variant.
Evidence considered
- Variant consequence is frameshift
Sources
PP2 N/APP2 is a missense-specific criterion. This variant is a frameshift deletion, so PP2 is not applicable. Details ▾Hide ▴
Rule
PP2 applies to missense variants in genes with a low rate of benign missense variation and where missense is a common disease mechanism.
Evidence considered
- Variant consequence is frameshift
Sources
PP3 N/AThis is a coding frameshift variant rather than a missense or noncoding splice-prediction case. SpliceAI shows a low maximum delta score of 0.03, but PTEN Expert Panel PP3 is intended for missense variants with REVEL >0.7 or splicing variants with concordant splice-prediction evidence, so PP3 is not applied. Details ▾Hide ▴
Rule
PP3 for PTEN applies to missense variants with REVEL >0.7 or splicing variants with concordant computational evidence.
Evidence considered
- Variant is frameshift
- SpliceAI max delta score is 0.03
- PTEN PP3 rule is for missense or splicing prediction contexts
Sources
PP4 N/AThe PTEN Expert Panel specification designates PP4 as not applicable. Details ▾Hide ▴
Rule
PTEN Expert Panel: PP4 not applicable.
Evidence considered
- PTEN Expert Panel specification lists PP4 as not applicable
Sources
PP5 N/AThe PTEN Expert Panel specification designates PP5 as not applicable. Details ▾Hide ▴
Rule
PTEN Expert Panel: PP5 not applicable.
Evidence considered
- PTEN Expert Panel specification lists PP5 as not applicable
Sources
BP1 N/AThe PTEN Expert Panel specification designates BP1 as not applicable. Details ▾Hide ▴
Rule
PTEN Expert Panel: BP1 not applicable.
Evidence considered
- PTEN Expert Panel specification lists BP1 as not applicable
Sources
BP3 N/AThe PTEN Expert Panel specification designates BP3 as not applicable. Details ▾Hide ▴
Rule
PTEN Expert Panel: BP3 not applicable.
Evidence considered
- PTEN Expert Panel specification lists BP3 as not applicable
Sources
BP4 N/AThis is a coding frameshift variant rather than a missense or noncoding splice-prediction case. SpliceAI predicts no significant splice impact with a maximum delta score of 0.03, but PTEN Expert Panel BP4 is intended for missense variants with REVEL <0.5 or splicing variants with concordant benign splice-prediction evidence, so BP4 is not applied. Details ▾Hide ▴
Rule
BP4 for PTEN applies to missense variants with REVEL <0.5 or splicing variants with concordant benign computational evidence.
Evidence considered
- Variant is frameshift
- SpliceAI max delta score is 0.03
- PTEN BP4 rule is for missense or splicing prediction contexts
Sources
BP6 N/AThe PTEN Expert Panel specification designates BP6 as not applicable. Details ▾Hide ▴
Rule
PTEN Expert Panel: BP6 not applicable.
Evidence considered
- PTEN Expert Panel specification lists BP6 as not applicable
Sources
BP7 N/ABP7 applies to synonymous or deep intronic variants. This variant is a coding frameshift deletion, so BP7 is not applicable. Details ▾Hide ▴
Rule
BP7 applies to synonymous or intronic variants at or beyond +7/-21 with no predicted splice impact.
Evidence considered
- Variant consequence is frameshift
Sources
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.548del
- Protein (HGVS p.)
- NP_000305.3:p.(Lys183ArgfsTer16)
- GRCh38
- chr10:87952170 TA>T
- GRCh37
- chr10:89711927 TA>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 is a coding frameshift variant rather than a missense or noncoding splice-prediction case. SpliceAI shows a low maximum delta score of 0.03, but PTEN Expert Panel PP3 is intended for missense variants with REVEL >0.7 or splicing variants with concordant splice-prediction evidence, so PP3 is not applied. Details ▾Hide ▴
Rule
PP3 for PTEN applies to missense variants with REVEL >0.7 or splicing variants with concordant computational evidence.
Evidence considered
- Variant is frameshift
- SpliceAI max delta score is 0.03
- PTEN PP3 rule is for missense or splicing prediction contexts
Sources
BP4 N/AThis is a coding frameshift variant rather than a missense or noncoding splice-prediction case. SpliceAI predicts no significant splice impact with a maximum delta score of 0.03, but PTEN Expert Panel BP4 is intended for missense variants with REVEL <0.5 or splicing variants with concordant benign splice-prediction evidence, so BP4 is not applied. Details ▾Hide ▴
Rule
BP4 for PTEN applies to missense variants with REVEL <0.5 or splicing variants with concordant benign computational evidence.
Evidence considered
- Variant is frameshift
- SpliceAI max delta score is 0.03
- PTEN BP4 rule is for missense or splicing prediction contexts
Sources
BP7 N/ABP7 applies to synonymous or deep intronic variants. This variant is a coding frameshift deletion, so BP7 is not applicable. Details ▾Hide ▴
Rule
BP7 applies to synonymous or intronic variants at or beyond +7/-21 with no predicted splice impact.
Evidence considered
- Variant consequence is frameshift
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
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/variation/486232/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89711927-TA-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87952170-TA-T?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.548d…
- OncoKB ↗www.oncokb.org/gene/PTEN/K183Rfs*16
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=117218398
- 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 has been reported in ClinVar as Pathogenic (1 clinical laboratory).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
Functional
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV64296982, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.