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.1300A>G (p.Asn434Asp)

Curation Version - 2.1
Curation History
JSON LD for Version 2.1

CA410147457

532666 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e4772815-842a-4b3b-97d3-d38e5c389d54

Approved on: 2025-02-24

Published on: 2025-02-24

HGVS expressions

NM_001754.5:c.1300A>G

NM_001754.5(RUNX1):c.1300A>G (p.Asn434Asp)

NC_000021.9:g.34792278T>C

CM000683.2:g.34792278T>C

NC_000021.8:g.36164575T>C

CM000683.1:g.36164575T>C

NC_000021.7:g.35086445T>C

NG_011402.2:g.1197434A>G

ENST00000675419.1:c.1300A>G

ENST00000300305.7:c.1300A>G

ENST00000344691.8:c.1219A>G

ENST00000399240.5:c.1027A>G

ENST00000437180.5:c.1300A>G

ENST00000482318.5:c.*890A>G

NM_001001890.2:c.1219A>G

NM_001754.4:c.1300A>G

NM_001001890.3:c.1219A>G

Uncertain Significance

PM2_Supporting BP4

PP4 PP1 PP3 PP2 PVS1 BA1 PM6 PM3 PM1 PM4 PM5 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP1 PS2 PS4 PS3 PS1

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 Version 2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.1300A>G (p.Asn434Asp) is a missense variant located in exon 9. This variant is absent from all population databases, including gnomAD v2.1.1 and gnomAD v3.1.2, which provide at least 20x coverage for the RUNX1 gene at this position (PM2_supporting). It has a REVEL score of 0.169 (≤0.50), and no evidence supports an impact on splicing, as indicated by a SpliceAI score of 0.00 (BP4). This variant has not been previously reported, and no pathogenic or likely pathogenic amino acid changes have been documented at the same residue. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BP4

This missense variant has a REVEL score ≤0.50 (0.169) and SpliceAI is ≤0.20 (0.00).

PP4

Not applicable

PP1

nil data

PP3

This missense variant has a REVEL score that is not ≥0.88 (0.169) and SpliceAI that is not ≥0.38 (0.00).

PP2

Not applicable

PVS1

variant is a missense variant and not within a splice site

BA1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

PM6

nil data

PM3

Not applicable

PM1

variant IS NOT one of the following amino acid residues within RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204

PM4

the variant is a missense variant

PM5

No pathogenic or likely pathogenic variants reported

BS2

Not applicable

BS4

nil data

BS3

To our knowledge, no in vitro or in vivo functional studies are available for this variant.

BS1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BP5

Not applicable

BP7

the variant is a missense variant

BP2

Not applicable

BP3

the variant is a missense variant

BP1

Not applicable

PS2

nil data

PS4

nil data

PS3

To our knowledge, no in vitro or in vivo functional studies are available for this variant.

PS1

No pathogenic or likely pathogenic variants reported

Curation History

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