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.239A>C (p.Glu80Ala)

CA410203825

658195 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f68df82b-90ff-451e-b236-704c38a2fa61

HGVS expressions

NM_001754.5:c.239A>C

NM_001754.5(RUNX1):c.239A>C (p.Glu80Ala)

NC_000021.9:g.34886955T>G

CM000683.2:g.34886955T>G

NC_000021.8:g.36259252T>G

CM000683.1:g.36259252T>G

NC_000021.7:g.35181122T>G

NG_011402.2:g.1102757A>C

ENST00000675419.1:c.239A>C

ENST00000300305.7:c.239A>C

ENST00000344691.8:c.158A>C

ENST00000358356.9:c.158A>C

ENST00000399237.6:c.203A>C

ENST00000399240.5:c.158A>C

ENST00000437180.5:c.239A>C

ENST00000455571.5:c.200A>C

ENST00000482318.5:c.59-6242A>C

NM_001001890.2:c.158A>C

NM_001122607.1:c.158A>C

NM_001754.4:c.239A>C

NM_001001890.3:c.158A>C

NM_001122607.2:c.158A>C

Uncertain Significance

PM6 PM2 PM5 PM1 PM3 PM4 PVS1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP7 BP5 PS4 PS2 PS1 PS3 BA1 PP4 PP1 PP3 PP2

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.239A>C (p.Glu80Ala) is a missense mutation. This variant has been seen three times in gnomADv2.1 at a MAF of 0.00001223 (0.001821%, 2/109846 in the European (Non-/finnish) sub-population). It does not meet any population criteria. The computational predictor REVEL gives a score of >0.50 (0.856). There is no predicted splice effect (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: No criteria are met.

PM6

No case study found

PM2

This variant has been seen three times in gnomADv2.1 at a MAF of 0.00001223 (0.001821%, 2/109846 in the European (Non-/finnish) sub-population). It does not meet any population criteria.

PM5

No pathogenic variant has been identified at this amino acid (a.a.80)

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

PVS1

Missense variant

BS2

This rule is not applicable for MM-VCEP

BS4

No case study found

BS3

No functional studies found

BS1

This variant has been seen three times in gnomADv2.1 at a MAF of 0.00001223 (0.001821%, 2/109846 in the European (Non-/finnish) sub-population). It does not meet any population criteria.

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP4

REVEL >0.50 (0.856)

BP1

This rule is not applicable for MM-VCEP

BP7

Missense variant

BP5

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.80)

PS3

No functional studies found

BA1

This variant has been seen three times in gnomADv2.1 at a MAF of 0.00001223 (0.001821%, 2/109846 in the European (Non-/finnish) sub-population). It does not meet any population criteria.

PP4

This rule is not applicable for MM-VCEP

PP1

No case study found

PP3

REVELscore is not ≥ 0.88 (0.856)

PP2

This rule is not applicable for MM-VCEP

Approved on: 2023-11-13

Published on: 2023-11-13

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