Variant: NM_001754.5(RUNX1):c.358G>A (p.Ala120Thr)

CA410202778

1057975 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 157ce88f-26ae-4a82-998a-c2c08bd944c5

Approved on: 2024-09-16

Published on: 2024-09-16

HGVS expressions

NM_001754.5:c.358G>A
NM_001754.5(RUNX1):c.358G>A (p.Ala120Thr)
NC_000021.9:g.34880707C>T
CM000683.2:g.34880707C>T
NC_000021.8:g.36253004C>T
CM000683.1:g.36253004C>T
NC_000021.7:g.35174874C>T
NG_011402.2:g.1109005G>A
ENST00000675419.1:c.358G>A
ENST00000300305.7:c.358G>A
ENST00000344691.8:c.277G>A
ENST00000358356.9:c.277G>A
ENST00000399237.6:c.322G>A
ENST00000399240.5:c.277G>A
ENST00000437180.5:c.358G>A
ENST00000455571.5:c.319G>A
ENST00000482318.5:c.65G>A
NM_001001890.2:c.277G>A
NM_001122607.1:c.277G>A
NM_001754.4:c.358G>A
NM_001001890.3:c.277G>A
NM_001122607.2:c.277G>A

Uncertain Significance

• Met criteria codes: PP3 PM1_Supporting PM2_Supporting

• Not Met criteria codes: PP1 PP4 PP2 PM5 PM3 PM4 PS4 PS2 PS1 PS3 PM6 BA1 PVS1 BP7 BP5 BP2 BP3 BP4 BP1 BS2 BS4 BS3 BS1

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

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.358G>A (p.Ala120Thr) is a missense variant which affects one of the hotspot residues in the RHD established by the MM-VCEP for RUNX1 (AA Val120) (PM1_supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant has a REVEL score > 0.88 (0.901) (PP3). This variant has been reported in ClinVar; however, no phenotypic data was provided. In summary, this variant meets the criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1_supporting, PP3, PM2_supporting.

Met criteria codes

• PP3: REVEL score ≥ 0.88 (REVEL score=0.901)
• PM1_Supporting: This missense variant affects amino acid 120 which is an amino acid residue (89-204) within the RHD.
• PM2_Supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting)

Not Met criteria codes

• PP1: No case study found
• PP4: This rule is not applicable for MM-VCEP
• PP2: This rule is not applicable for MM-VCEP
• PM5: No missense change has been at amino acid 120 has been determined to be pathogenic before
• PM3: This rule is not applicable for MM-VCEP
• PM4: This is a missense variant
• PS4: No proband meeting RUNX1 FPD-MM phenotypic criteria has been described
• PS2: No case study found
• PS1: No missense change has been at amino acid 120 has been determined to be pathogenic before
• PS3: No studies found
• PM6: No case study found
• BA1: PM2 Met
• PVS1: This is a missense variant
• BP7: No splice effect predicted
• BP5: This rule is not applicable for MM-VCEP
• BP2: No case study found
• BP3: This rule is not applicable for MM-VCEP
• BP4: PP3 Met
• BP1: This rule is not applicable for MM-VCEP
• BS2: This rule is not applicable for MM-VCEP
• BS4: No case study found
• BS3: No studies found
• BS1: PM2 Met