Variant: NM_001754.5(RUNX1):c.447A>C (p.Ala149=)

CA512318720

1142684 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: fdc5cdaa-936b-42dd-9c1c-ffb4c241a00a

Approved on: 2022-07-06

Published on: 2022-07-06

HGVS expressions

NM_001754.5:c.447A>C
NM_001754.5(RUNX1):c.447A>C (p.Ala149=)
NC_000021.9:g.34880618T>G
CM000683.2:g.34880618T>G
NC_000021.8:g.36252915T>G
CM000683.1:g.36252915T>G
NC_000021.7:g.35174785T>G
NG_011402.2:g.1109094A>C
ENST00000675419.1:c.447A>C
ENST00000300305.7:c.447A>C
ENST00000344691.8:c.366A>C
ENST00000358356.9:c.366A>C
ENST00000399237.6:c.411A>C
ENST00000399240.5:c.366A>C
ENST00000437180.5:c.447A>C
ENST00000455571.5:c.408A>C
ENST00000482318.5:c.*37A>C
NM_001001890.2:c.366A>C
NM_001122607.1:c.366A>C
NM_001754.4:c.447A>C
NM_001001890.3:c.366A>C
NM_001122607.2:c.366A>C

Uncertain Significance

• Met criteria codes: PM2_Supporting BP4

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

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.447A>C (p.Ala149=) is a synonymous variant. No REVEL score because a synonymous variant and SpliceAI is ≤0.20 (BP4). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets the criteria to be classified as a variant of Uncertain significance - insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and PM2_supporting.

Met criteria codes

• PM2_Supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2)
• BP4: No REVEL score. SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).

Not Met criteria codes

• BS2: This rule is not applicable for MM-VCEP
• BS4: No case studies found
• BS3: No evidence found
• BS1: Meets PM2_supporting
• PVS1: N/A
• BP5: This rule is not applicable for MM-VCEP
• BP7: The c.447A>C (p.Ala149=) variant is a synonymous (silent) variant. SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20). Evolutionary algorithms predict site is conserved - PhyloP score 4.9
• BP2: No homozygotes observed in gnomAD population (v2 and v3)
• BP3: This rule is not applicable for MM-VCEP
• BP1: This rule is not applicable for MM-VCEP
• PS2: No case studies found
• PS4: No case studies found
• PS3: No evidence found
• PS1: N/A
• PP4: N/A
• PP1: No case studies found
• PP3: SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
• PP2: This rule is not applicable for MM-VCEP
• BA1: Meets PM2_supporting
• PM3: This rule is not applicable for MM-VCEP
• PM1: N/A
• PM4: N/A
• PM5: N/A
• PM6: No case studies found