Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_001754.5(RUNX1):c.449C>A (p.Ala150Asp)

CA410202586

1713291 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 30f9d8af-9a3e-4aa0-9095-c09f2e45821a
Approved on: 2024-07-25
Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.449C>A
NM_001754.5(RUNX1):c.449C>A (p.Ala150Asp)
NC_000021.9:g.34880616G>T
CM000683.2:g.34880616G>T
NC_000021.8:g.36252913G>T
CM000683.1:g.36252913G>T
NC_000021.7:g.35174783G>T
NG_011402.2:g.1109096C>A
ENST00000675419.1:c.449C>A
ENST00000300305.7:c.449C>A
ENST00000344691.8:c.368C>A
ENST00000358356.9:c.368C>A
ENST00000399237.6:c.413C>A
ENST00000399240.5:c.368C>A
ENST00000437180.5:c.449C>A
ENST00000455571.5:c.410C>A
ENST00000482318.5:c.*39C>A
NM_001001890.2:c.368C>A
NM_001122607.1:c.368C>A
NM_001754.4:c.449C>A
NM_001001890.3:c.368C>A
NM_001122607.2:c.368C>A

Uncertain Significance

Met criteria codes 2
PM2_Supporting PM1_Supporting
Not Met criteria codes 24
BP7 BP5 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 PVS1 PP1 PP4 PP3 PP2 PM6 PM5 PM3 PM4 BA1 BS4 BS3 BS1 BS2

Evidence Links 0

Expert Panel

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.449C>A (p.Ala150Asp) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant is located within the Runt Homology Domain (AA 89-204), but does not occur in an established hotspot residue (PM1_supporting). 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: PM1_supporting, PM2_supporting.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v3.2.1.
PM1_Supporting
This variant is found within the RUNX1 functional domain (residues 89 to 204).
Not Met criteria codes
BP7
This is a missense variant.
BP5
This rule is not applicable for MM.VCEP.
BP2
No studies have included this variant.
BP3
This rule is not applicable for MM.VCEP.
BP4
The REVEL score for this variant is 0.756 which is above the risk threshold for benign variants (<0.3). The SpliceAI score is 0 indicating that there is very little chance the this variant impacts splicing.
BP1
This rule is not applicable for MM.VCEP.
PS2
No studies have included this variant.
PS4
No studies have included this variant.
PS3
No studies have included this variant.
PS1
The current variant is the only variant found in this codon in ClinVar.
PVS1
This is a missense variant.
PP1
No studies have included this variant.
PP4
This rule is not applicable for MM.VCEP.
PP3
The REVEL score for this variant is 0.756 which is below the threshold for pathogenicity (>0.88). The SpliceAI score is 0.
PP2
This rule is not applicable for MM.VCEP.
PM6
No studies have included this variant.
PM5
The current variant is the only variant found in this codon in ClinVar.
PM3
This rule is not applicable for MM.VCEP.
PM4
This is a missense variant.
BA1
This variant is absent from gnomAD v2.1.1 and v3.2.1.
BS4
No studies have included this variant.
BS3
No studies have included this variant.
BS1
This variant is absent from gnomAD v2.1.1 and v3.2.1.
BS2
This rule is not applicable for MM.VCEP.
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