Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001754.5(RUNX1):c.891_904del (p.Pro298fs)

CA2739267612

2839740 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: 25352593-9a9f-44c1-9037-0e4eb472ac58

Approved on: 2026-10-05

Published on: 2026-10-05

HGVS expressions

NM_001754.5(RUNX1):c.891_904del (p.Pro298fs)

NM_001754.5:c.891_904del

NC_000021.9:g.34799366_34799379del

CM000683.2:g.34799366_34799379del

NC_000021.8:g.36171663_36171676del

CM000683.1:g.36171663_36171676del

NC_000021.7:g.35093533_35093546del

NG_011402.2:g.1190335_1190348del

ENST00000675419.1:c.891_904del

ENST00000300305.7:c.891_904del

ENST00000344691.8:c.810_823del

ENST00000399240.5:c.618_631del

ENST00000437180.5:c.891_904del

ENST00000482318.5:c.*481_*494del

NM_001001890.2:c.810_823del

NM_001754.4:c.891_904del

NM_001001890.3:c.810_823del

Likely Pathogenic

PM2_Supporting PM5_Supporting PVS1_Strong

PS2 PS4 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM6 PM1 PM3 PM4 BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP3 BP4 BP1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RUNX1 Version 3.1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.891_904del (p.Pro298Phefs*297) is a frameshift variant which is not predicted to undergo NMD (PVS1_Strong). This variant is downstream of c.98 (PM5_Supporting) and is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_Strong, PM5_Supporting, PM2_Supporting.

PM2_Supporting

Completely absent from gnomAD v2+v3+v4 with a mean coverage of at least 20X.

PM5_Supporting

Other nonsense/frameshift variants have been reported as pathogenic/likely pathogenic in exon 8 (PMID: 35764482).

PVS1_Strong

This variant is not predicted to undergo NMD, and the truncated/altered region is critical for protein function (frameshift (-) c.759-c.1440 as per VCEP specifications) (PVS1_Strong).

PS2

No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PS4

Proband data for this variant has not been reported in literature.

PS3

No relevant literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

Completely absent from gnomAD v2+v3+v4 with a mean coverage of at least 20X.

PP1

Segregation data for this variant has not been reported in literature.

PP4

Not applicable

PP3

This variant does not have applicable in-silico data available.

PP2

This rule is not applicable for MM-VCEP.

PM6

No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PM1

This variant is not a missense variant.

PM3

This rule is not applicable for MM-VCEP.

PM4

This variant is not an in-frame deletion/insertion.

BS4

Segregation data for this variant has not been reported in literature.

BS3

No relevant literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

BS1

Completely absent from gnomAD v2+v3+v4 with a mean coverage of at least 20X.

BS2

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for MM-VCEP.

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

BP3

This rule is not applicable for MM-VCEP.

BP4

This variant does not have applicable in-silico data available.

BP1

This rule is not applicable for MM-VCEP.

Curation History

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