Variant: NM_001754.4(RUNX1):c.861C>A (p.Tyr287Ter)

CA248619

14467 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: fed802a7-8c1d-4396-89f1-65546e996764

Approved on: 2019-07-29

Published on: 2019-08-02

HGVS expressions

NM_001754.4:c.861C>A
NM_001754.4(RUNX1):c.861C>A (p.Tyr287Ter)
NC_000021.9:g.34799407G>T
CM000683.2:g.34799407G>T
NC_000021.8:g.36171704G>T
CM000683.1:g.36171704G>T
NC_000021.7:g.35093574G>T
NG_011402.2:g.1190305C>A
ENST00000675419.1:c.861C>A
ENST00000300305.7:c.861C>A
ENST00000344691.8:c.780C>A
ENST00000399240.5:c.588C>A
ENST00000437180.5:c.861C>A
ENST00000482318.5:c.*451C>A
NM_001001890.2:c.780C>A
NM_001001890.3:c.780C>A
NM_001754.5:c.861C>A

Pathogenic

• Met criteria codes: PM2 PVS1 PS4_Supporting PP1_Strong

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

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The NM_001754.4:c.861C>A (p.Tyr287Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant was found to co-segregate with disease in multiple affected family members, with seven meioses observed in one family (PP1_Strong; PMID: 11830488). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). The variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 11830488). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PP1_Strong, PM2, PS4_Supporting.

Met criteria codes

• PM2: The variant is absent from all population databases.
• PVS1: Nonsense variant before the c.916 cutoff that predict to undergo NMD
• PS4_Supporting: One family with FPD/AML.
• PP1_Strong: At least 7 meioses in the family with FPD/AML.

Not Met criteria codes

• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline