Starting
Initialising…
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PTEN
Final classification
Likely Pathogenic
PTEN c.634+1G>C · p.?
PTEN

The PTEN c.634+1G>C (p.?) variant has been observed in somatic cancers in COSMIC (COSV64295775; 2 occurrences) and has been reported in ClinVar as pathogenic by three clinical laboratories.

Gene
PTEN
Transcript
NM_000314.8
HGVS · transcript:coding
NM_000314.8:c.634+1G>C
Consequence
N/A
GRCh38
chr10:87952260 G>C
GRCh37
chr10:89712017 G>C
Basis PTEN CSPEC/VCEP final-classification framework from final_classification_framework.json (criteria-combination rules; Richards et al. 2015 combining rules as implemented in the CSPEC ruleset). ▾
PTEN CSPEC/VCEP final-classification framework from final_classification_framework.json (criteria-combination rules; Richards et al. 2015 combining rules as implemented in the CSPEC ruleset).
Classification rationale
PVS1PM2 Likely Pathogenic
PTEN c.634+1G>C

The PTEN c.634+1G>C (p.?) variant has been observed in somatic cancers in COSMIC (COSV64295775; 2 occurrences) and has been reported in ClinVar as pathogenic by three clinical laboratories.1 This variant is absent from gnomAD v2.1 and gnomAD v4.1.2 In silico splicing analysis predicts a marked effect on RNA processing, with a SpliceAI maximum delta score of 0.99, consistent with disruption of the canonical donor site.3

PVS1 + PM2 → Likely Pathogenic
1 cosmicclinvar ↗
2 gnomad_v2 ↗gnomad_v4 ↗
3 spliceai ↗
Gene diagram · NM_000314.8 · variants mapped to exon structure
PTEN NM_000314.8
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.
      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 v4 ↗ gnomAD v2 ↗
      ClinVar screenshot
      ClinVar
      This variant has been reported in ClinVar as Pathogenic (3 clinical laboratories).
      ClinVar ↗
      SpliceAI screenshot
      In silico
      SpliceAI predicts possible splice impact for this variant (max delta score = 0.99).
      SpliceAI ↗
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Somatic evidence
      COSMIC
      This variant has previously been reported in somatic cancers (COSMIC; COSV64295775, n = 2 times).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      Literature · how each cited paper was used
      2papers cited
      Each card is an audit: what was searched, what was found, whether it names the variant, which criteria it fed, and why.
      ACG clinical guideline: Genetic testing and management of hereditary gastrointes
      PMID 25645574 ↗
      Found
      Structured finding pending for this record — see source link.
      Applied to
      →PVS1 supports · met
      Characterization of cryptic splicing in germline PTEN intronic variants in Cowde
      PMID 28677221 ↗
      Found
      Structured finding pending for this record — see source link.
      Applied to
      →PVS1 supports · met
      Sources & reference links
      6Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB