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LYFE SCIENCES
Project: HERA
NM_001754.4:c.617dup
p.His206GlnfsTer7  ·  RUNX1
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Classification rationale
1

The RUNX1 c.617dup (p.His206GlnfsTer7; p.H206Qfs*7) variant has not been reported in ClinVar, and OncoKB lists p.H206Qfs*7 as Likely Oncogenic with a likely loss-of-function effect.

clinvar ↗ oncokb ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, which supports rarity in the general population and is below the RUNX1 PM2_supporting threshold of 0.00005.

cspec ↗ gnomad_v2 ↗ gnomad_v4 ↗
3

This variant is a truncating frameshift, and the RUNX1 MM-VCEP framework recognizes loss of function as an established disease mechanism for RUNX1; the available PVS1 assessment supports full-strength PVS1 for this variant.

cspec ↗
4

SpliceAI predicts no significant splice effect, with a maximum delta score of 0.02, which is below the 0.20 threshold and is consistent with the RUNX1 PM5_supporting rule for downstream nonsense or frameshift variants.

cspec ↗ 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
—
—
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.
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 = 0.02).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueH206
Hotspots ↗