Variant: NM_001754.5(RUNX1):c.1076C>T (p.Pro359Leu)

CA410148207

1951248 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 4e2d6630-95cc-4d07-a515-a5563d1952e5

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.1076C>T
NM_001754.5(RUNX1):c.1076C>T (p.Pro359Leu)
NC_000021.9:g.34792502G>A
CM000683.2:g.34792502G>A
NC_000021.8:g.36164799G>A
CM000683.1:g.36164799G>A
NC_000021.7:g.35086669G>A
NG_011402.2:g.1197210C>T
ENST00000675419.1:c.1076C>T
ENST00000300305.7:c.1076C>T
ENST00000344691.8:c.995C>T
ENST00000399240.5:c.803C>T
ENST00000437180.5:c.1076C>T
ENST00000482318.5:c.*666C>T
NM_001001890.2:c.995C>T
NM_001754.4:c.1076C>T
NM_001001890.3:c.995C>T

Uncertain Significance

• Met criteria codes: PM2

• Not Met criteria codes: BS2 BS4 BS3 BS1 BP3 BP2 BP4 BP1 BP7 BP5 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM6 PM4 PM3 PM1 PM5 PVS1

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.1076C>T (p.Pro359Leu) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, the clinical significance of this variant is uncertain due to insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting.

Met criteria codes

• PM2: absent from gnomAD V2 and V3 This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

Not Met criteria codes

• BS2: Not applicable.
• BS4: No data.
• BS3: No data.
• BS1: absent from gnomAD V2 and V3
• BP3: Not applicable (missense).
• BP2: No data.
• BP4: REVEL: 0.539; SpliceAI: Δ score 0.00
• BP1: Not applicable
• BP7: Not applicable (missense).
• BP5: Not applicable.
• PS2: No data.
• PS4: No data.
• PS3: No data.
• PS1: No data.
• BA1: absent from gnomAD V2 and V3
• PP4: Not applicable.
• PP1: No data.
• PP3: REVEL: 0.539 phyloP100way: 9.311
• PP2: Not applicable
• PM6: No data.
• PM4: Not applicable (missense).
• PM3: Not applicable.
• PM1: not located in a hot spot/critical region
• PM5: No relevant data existing. A different missense change at the same amino acid residue (P359R) was reported by Li Y et al, J Clin Invest. 2021, 131(17):e147898. However, this was classified as VUS.
• PVS1: Not applicable (missense).