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LYFE SCIENCES
Project: HERA
NM_000314.8:c.548del
p.Lys183ArgfsTer16  ·  PTEN
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Classification rationale
1

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.

clinvar ↗
2

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%).

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

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.

cspec ↗
4

SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.03.

spliceai ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Pathogenic (1 clinical laboratory).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Likely Oncogenic
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV64296982, n = 1 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueK183
Hotspots ↗