Variant: NM_001754.5(RUNX1):c.861C>T (p.Tyr287=)

CA512232261

760670 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: e65e412f-fea3-4389-88ee-deec84a55e32

Approved on: 2024-08-12

Published on: 2024-08-12

HGVS expressions

NM_001754.5:c.861C>T
NM_001754.5(RUNX1):c.861C>T (p.Tyr287=)
NC_000021.9:g.34799407G>A
CM000683.2:g.34799407G>A
NC_000021.8:g.36171704G>A
CM000683.1:g.36171704G>A
NC_000021.7:g.35093574G>A
NG_011402.2:g.1190305C>T
ENST00000675419.1:c.861C>T
ENST00000300305.7:c.861C>T
ENST00000344691.8:c.780C>T
ENST00000399240.5:c.588C>T
ENST00000437180.5:c.861C>T
ENST00000482318.5:c.*451C>T
NM_001001890.2:c.780C>T
NM_001754.4:c.861C>T
NM_001001890.3:c.780C>T

Uncertain Significance

• Met criteria codes: BP4 PM2_Supporting

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

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.861C>T (p.Tyr287=) is a synonymous variant which has a SpliceAI Δ score ≤ 0.20 (0.00) (BP4). This variant 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. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM2_Supporting.

Met criteria codes

• BP4: This synonymous variant has a SpliceAI Δ score ≤ 0.20 (0.00) (BP4).
• PM2_Supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

Not Met criteria codes

• BS2: This rule is not applicable for MM-VCEP.
• PVS1: This is a synonymous variant not at canonical +/- 1 or 2 splice sites and not known to cause loss of function.
• BS4: There are no published cases of this synonymous variant.
• BS3: There are no reported functional studies for this variant.
• BS1: This variant meets PM2.
• BP2: There are no published cases of this synonymous variant observed with a pathogenic variant.
• BP3: This rule is not applicable for MM-VCEP.
• BP1: This rule is not applicable for MM-VCEP.
• BP7: This synonymous variant is not predicted to be conserved with evolutionary conservation prediction algorithms (PhyloP score 2.97502 is more than 2.0). It is not found in other primates or at least 3 mammals.
• BP5: This rule is not applicable for MM-VCEP.
• PS2: There are no published cases of this synonymous variant.
• PS4: There are no published cases of this synonymous variant.
• PS3: There are no reported functional studies for this variant.
• PS1: This is a synonymous variant.
• PP1: There are no published cases of this synonymous variant.
• PP4: This rule is not applicable for MM-VCEP.
• PP3: This variant meets BP4.
• PP2: This rule is not applicable for MM-VCEP.
• PM1: This is a synonymous variant.
• PM5: This is a synonymous variant.
• PM3: This rule is not applicable for MM-VCEP.
• PM4: This synonymous variant does not change protein length.
• PM6: There are no published cases of this synonymous variant.
• BA1: This variant meets PM2.