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.965del (p.Leu321_Ser322insTer)

CA2573157369

1460663 (ClinVar)

Gene: RUNX1 (HGNC:861)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: ebe7d39f-0b88-4af9-a8d3-5c53ab3d0a9a

Approved on: 2026-10-05

Published on: 2026-10-05

HGVS expressions

NM_001754.5(RUNX1):c.965del (p.Leu321_Ser322insTer)

NM_001754.5:c.965del

NC_000021.9:g.34799303del

CM000683.2:g.34799303del

NC_000021.8:g.36171600del

CM000683.1:g.36171600del

NC_000021.7:g.35093470del

NG_011402.2:g.1190409del

ENST00000675419.1:c.965del

ENST00000300305.7:c.965del

ENST00000344691.8:c.884del

ENST00000399240.5:c.692del

ENST00000437180.5:c.965del

ENST00000482318.5:c.*555del

NM_001001890.2:c.884del

NM_001754.4:c.965del

NM_001001890.3:c.884del

Likely Pathogenic

PM2_Supporting PM5_Supporting PVS1_Strong

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

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.965del (p.Ser322Ter) is a nonsense 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

This variant is absent from gnomAD v.3.1.2 and gnomAD v2.1.1 which have at least 20x coverage for RUNX1 (PM2_supporting).

PM5_Supporting

This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting).

PVS1_Strong

This variant is not predicted to undergo NMD, and the truncated/altered region is critical for protein function (nonsense c.917-c.1440 as per VCEP specifications) (PVS1_Strong).

BS2

This rule is not applicable for the MM.VCEP.

BS4

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

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS1

This variant is absent from gnomAD v.3.1.2 and gnomAD v2.1.1 which have at least 20x coverage for RUNX1 (PM2_supporting).

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 the MM.VCEP.

BP4

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

BP1

This rule is not applicable for the MM.VCEP.

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for the MM.VCEP.

PM1

This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.

PM3

This rule is not applicable for the MM.VCEP.

PM4

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

PS2

De novo data for this variant has not been reported in literature.

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

BA1

This variant is absent from gnomAD v.3.1.2 and gnomAD v2.1.1 which have at least 20x coverage for RUNX1 (PM2_supporting).

PM6

De novo data for this variant has not been reported in literature.

PP1

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

PP4

This rule is not applicable for the MM.VCEP.

PP3

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

PP2

This rule is not applicable for the MM.VCEP.

Curation History

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