Starting
Initialising…
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RUNX1
Final classification
Pathogenic
RUNX1 c.529_551dup · p.Gln185SerfsTer34
RUNX1

The RUNX1 c.529_551dup (p.(Gln185SerfsTer34)) variant has not been observed in COSMIC and has not been reported in ClinVar; OncoKB classifies this variant as Likely Oncogenic with a likely loss-of-function effect.

Gene
RUNX1
Transcript
NM_001754.4
HGVS · transcript:coding
NM_001754.4:c.529_551dup
Consequence
N/A
GRCh38
chr21:34859535 C>CGGTGGGTTTGTGAAGACAGTGAT
GRCh37
chr21:36231832 C>CGGTGGGTTTGTGAAGACAGTGAT
Basis RUNX1 MM-VCEP/CSPEC point-based final-classification framework (Tavtigian et al., 2020 Bayesian point system; version 3.1.0). Applied points: PVS1_Very Strong = 8, PM2_Supporting = 1, PM5_Supporting = 1; total = 10 points.
RUNX1 MM-VCEP/CSPEC point-based final-classification framework (Tavtigian et al., 2020 Bayesian point system; version 3.1.0). Applied points: PVS1_Very Strong = 8, PM2_Supporting = 1, PM5_Supporting = 1; total = 10 points.
Classification rationale
PVS1PM2PM5 Pathogenic
RUNX1 c.529_551dup

The RUNX1 c.529_551dup (p.(Gln185SerfsTer34)) variant has not been observed in COSMIC and has not been reported in ClinVar; OncoKB classifies this variant as Likely Oncogenic with a likely loss-of-function effect.1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, so the observed allele frequency is 0, which is below the RUNX1 MM-VCEP PM2_Supporting threshold of less than or equal to 0.00005.2 This duplication is predicted to cause a frameshift, p.(Gln185SerfsTer34), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, which is consistent with applying PVS1 and PM5_Supporting under the RUNX1 MM-VCEP framework.3

PVS1 + PM2 + PM5 Pathogenic
Gene diagram · NM_001754.4 · variants mapped to exon structure
RUNX1 NM_001754.4
Fetching transcript structure from UCSC…
Applied criteria · 3 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.
      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 = 0.01).
      Functional / OncoKB screenshot
      Functional Likely Oncogenic
      OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
      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
      8Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC
      Cancer hotspots