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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001754.5(RUNX1):c.899C>T (p.Thr300Met)

CA10014273

409809 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b0d433bc-d13c-413f-877d-554f4902abb1

Approved on: 2023-11-13

Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.899C>T

NM_001754.5(RUNX1):c.899C>T (p.Thr300Met)

NC_000021.9:g.34799369G>A

CM000683.2:g.34799369G>A

NC_000021.8:g.36171666G>A

CM000683.1:g.36171666G>A

NC_000021.7:g.35093536G>A

NG_011402.2:g.1190343C>T

ENST00000675419.1:c.899C>T

ENST00000300305.7:c.899C>T

ENST00000344691.8:c.818C>T

ENST00000399240.5:c.626C>T

ENST00000437180.5:c.899C>T

ENST00000482318.5:c.*489C>T

NM_001001890.2:c.818C>T

NM_001754.4:c.899C>T

NM_001001890.3:c.818C>T

Uncertain Significance

BP4

BS4 BS3 BS1 BS2 PVS1 BP7 BP5 BP2 BP3 BP1 PS4 PS2 PS1 PS3 BA1 PP4 PP1 PP3 PP2 PM5 PM1 PM3 PM4 PM6 PM2

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.899C>T (p.Thr300Met) is a missense variant. This variant has been seen in gnomADv2.1 at a MAF of 0.00005274 (0.005274%, 6/113766 in the European(non-Finnish) sub-population). This variant does not meet any population criteria. This missense variant has a REVEL score <0.50 (0.423)(BP4). There is no splicing effect predicted (SpliceAI=0). The variant has not been reported in patients with the RUNX1-defined phenotype. 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: BP4

BP4

This missense variant has a REVEL score <0.50 (0.423).

BS4

No case study found

BS3

No functional studies found

BS1

This variant has been seen in gnomADv2.1 at a MAF of 0.00005274 (0.005274%, 6/113766 in the European(non-Finnish) sub-population). This variant does not meet any population criteria.

BS2

This rule is not applicable for MM-VCEP

PVS1

Missense variant

BP7

Missense variant

BP5

This rule is not applicable for MM-VCEP

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

PS4

No case study found

PS2

No case study found

PS1

No pathogenic variant has been identified at this amino acid (a.a. 300)

PS3

No functional studies found

BA1

This variant has been seen in gnomADv2.1 at a MAF of 0.00005274 (0.005274%, 6/113766 in the European(non-Finnish) sub-population). This variant does not meet any population criteria.

PP4

This rule is not applicable for MM-VCEP

PP1

No case study found

PP3

BP4 Met

PP2

This rule is not applicable for MM-VCEP

PM5

No pathogenic variant has been identified at this amino acid (a.a. 300)

PM1

This variant does not affect one of the hotspot residues established by the MM-VCEP for RUNX1

PM3

This rule is not applicable for MM-VCEP

PM4

Missense variant

PM6

No case study found

PM2

This variant has been seen in gnomADv2.1 at a MAF of 0.00005274 (0.005274%, 6/113766 in the European(non-Finnish) sub-population). This variant does not meet any population criteria.

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