Starting
Initialising…
0%
Legacy Engine
Processing…
Classification rationale
1

NM_000314.8:c.348del predicts PTEN p.(Asp116GlufsTer18), a frameshift expected to truncate the protein early in exon 5.

2

The PTEN PVS1 decision tree assigns PVS1 to frameshift variants in NM_000314.8 when the stop/disruption occurs at or 5' to p.D375 (c.1121); this variant truncates at p.Asp116fs, which is well upstream of that threshold and is consistent with loss of function.

3

The variant is absent from gnomAD v2.1 and gnomAD v4.1, and the PTEN specification applies PM2 at Supporting strength for variants with allele frequency below 0.00001, with a subpopulation threshold below 0.00002 when multiple alleles are present.

cspec ↗
4

No PTEN-specific final classification framework was retrieved, so the generic ACMG/AMP combination rules were used as fallback; with PVS1 and PM2_Supporting alone, this evidence set does not reach a defined pathogenic or likely pathogenic combination under those rules, and the variant is therefore classified as a variant of uncertain significance pending human review.

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
Rationale
Select a criterion to inspect its explanation.
Evidence used
Gaps remaining
Rule
Publications
Research and evidence
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
Functional evidence
03
Functional
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
COSMIC evidence
05
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV64292521, n = 2 times).
Cancer hotspots evidence
06
Cancer hotspots
No cancer hotspot summary recorded.