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This report is still being assembled — sections appear as each stage finishes. It isn't final yet.
PTEN
Final classification
Likely Pathogenic
PTEN c.33_54del · p.Asn12MetfsTer5
PTEN

NM_000314.6:c.33_54del is a 22 bp deletion in exon 1 of PTEN causing a frameshift (p.Asn12MetfsTer5) predicted to undergo nonsense-mediated decay, assigned PVS1 at very strong strength under the PTEN VCEP decision tree.

Gene
PTEN
Transcript
NM_000314.6
HGVS · transcript:coding
NM_000314.6:c.33_54del
Consequence
N/A
GRCh38
chr10:87864499 CAGAAACAAAAGGAGATATCAAG>C
GRCh37
chr10:89624256 CAGAAACAAAAGGAGATATCAAG>C
Basis 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.
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.
Classification rationale
PVS1PM2 Likely Pathogenic
PTEN c.33_54del

NM_000314.6:c.33_54del is a 22 bp deletion in exon 1 of PTEN causing a frameshift (p.Asn12MetfsTer5) predicted to undergo nonsense-mediated decay, assigned PVS1 at very strong strength under the PTEN VCEP decision tree.1 The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, meeting PM2 at supporting strength under PTEN VCEP specifications.2 The variant is absent from ClinVar; no functional studies, segregation data, case observations, or de novo reports were identified in the reviewed literature.3 Under the PTEN VCEP combination rules (Rule20, pathogenic track), PVS1 (Very Strong) plus one Supporting criterion (PM2_Supporting) yields a final classification of Likely Pathogenic.4

PVS1 + PM2 Likely Pathogenic
1 cspec ↗pvs1_gene_contextpvs1_variant_assessment
Gene diagram · NM_000314.6 · variants mapped to exon structure
PTEN NM_000314.6
Fetching transcript structure from UCSC…
Applied criteria · 2 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      Research & evidence
      Population frequency · supports pathogenic
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      v4.1
      Absent from gnomAD v4.1.
      v2.1
      Absent from gnomAD v2.1.
      🇨🇦 CA
      Absent from gnomAD-Canada v1.0.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD v4.1
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD v2.1
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD Canada 🇨🇦
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      ClinVar screenshot
      ClinVar
      This variant is absent from ClinVar.
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.13).
      Functional / OncoKB screenshot
      Functional Likely Oncogenic
      OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Cancer hotspots screenshot
      Cancer hotspots
      Somatic evidence Not in COSMIC / hotspots
      COSMIC
      This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant hotspot.
      Sources & reference links
      9Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      gnomAD-Canada
      SpliceAI
      OncoKB
      COSMIC
      Cancer hotspots
      Triaged references · 2 PMIDs not cited in assessment
      11237521 ↗ PTEN: life as a tumor suppressor. ONCOKB
      17218262 ↗ Essential role for nuclear PTEN in maintaining chromosomal integrity. ONCOKB