Starting

Initialising…

RUNX1

Final classification

Likely Benign

RUNX1 c.1113C>T · p.Ala371=

RUNX1

Gene

RUNX1

Transcript

NM_001001890.2

HGVS · transcript:coding

NM_001001890.2:c.1113C>T

Consequence

N/A

GRCh38

chr21:34792384 G>A

GRCh37

chr21:36164681 G>A

Basis Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v3.1.0 point-based framework: PM2 supporting (+1) + BP4 supporting (-1) + BP7 supporting (-1) = -1 points, which maps to Likely Benign. ▾

Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v3.1.0 point-based framework: PM2 supporting (+1) + BP4 supporting (-1) + BP7 supporting (-1) = -1 points, which maps to Likely Benign.

Classification rationale

PM2 BP4BP7 Likely Benign

RUNX1 c.1113C>T

The RUNX1 c.1113C>T (p.Ala371=; p.A371=) variant has been reported in ClinVar, where the aggregate record is Uncertain Significance with expert panel review and includes two likely benign laboratory submissions.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, placing the observed population frequency at 0 and below the RUNX1 PM2_supporting threshold of 0.00005.² SpliceAI predicts no significant splice effect with a maximum delta score of 0.00, which is below the RUNX1 PP3 threshold of 0.38 and at or below the BP4 and BP7 threshold of 0.20 for synonymous variants.³

PM2 + BP4 + BP7 → Likely Benign

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗

3 spliceai ↗cspec ↗

Gene diagram · NM_001001890.2 · variants mapped to exon structure

RUNX1 NM_001001890.2

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

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency · supports benign

gnomAD v4.1

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

This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Uncertain Significance by ClinGen Myeloid Malignancy Variant Curation Expert Panel (expert panel).

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

OncoKB ↗

COSMIC

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.

COSMIC ↗ Hotspots ↗

Sources & reference links

8Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots