Genetic Information

Gene & Transcript Details

Gene
RUNX1
Transcript
NM_001001890.2 MANE Select
Total Exons
—
Reference Sequence
NC_000021.8
Alternative Transcripts
IDStatusDetails
NM_001001890.1 Alternative 7288 nt | 1579–2940
NM_001001890.3 Alternative 7283 nt | 1588–2949
NM_001001890.2 Alternative 7274 nt | 1579–2940

Variant Details

HGVS Notation
NM_001001890.2:c.319_323del
Protein Change
A107Qfs*2
Location
Exon 2 (Exon 2 of )
2
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Pathogenic
1 publications
Publications List
PMID: 18723428

This sequence change creates a premature translational stop signal (p.Ala134Glnfs*2) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. For these reasons, this variant has been classified as Pathogenic.

Clinical Statement

"This variant has been reported in ClinVar as Pathogenic (1 clinical laboratories) and as Pathogenic by ClinGen Myeloid Malignancy Variant Curation Expert Panel expert panel."

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene RUNX1.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: RUNX1A107Qfs*2RUNX1A107Qfs*2SomaticNCBI Gene:861|Show additional gene information Variant OverviewRUNX1, a transcription factor involved in hematopoietic differentiation, is altered by mutation or chromosomal rearrangement in various hematologic malignancies.The RUNX1 A107Qfs*2 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in RUNX1 is: Truncating mutations in RUNX1 are most commonly caused by chromosomal translocations that result in a truncation and fusion of RUNX1 to heterologous proteins, inhibiting its function, and predisposing to certain types of leukemia, lymphomas, and myelodysplastic syndromes (PMID: 15386419, 17394134, 15864279). JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Unknown
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.01 53 bp
- Donor Loss (DL) 0.03 -80 bp
+ Acceptor Gain (AG) 0.0 40 bp
+ Donor Gain (DG) 0.0 -203 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PVS1

PVS1 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PP5

PP5 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)