Variant: NM_001754.4(RUNX1):c.557T>A (p.Val186Asp)

CA248819

212089 (ClinVar)

Gene: RUNX1

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

Inheritance Mode: Autosomal dominant inheritance

UUID: 3ff9a59f-f463-4e1a-942e-a60afc15686a

HGVS expressions

NM_001754.4:c.557T>A
NM_001754.4(RUNX1):c.557T>A (p.Val186Asp)
NC_000021.9:g.34859530A>T
CM000683.2:g.34859530A>T
NC_000021.8:g.36231827A>T
CM000683.1:g.36231827A>T
NC_000021.7:g.35153697A>T
NG_011402.2:g.1130182T>A
NM_001001890.2:c.476T>A
NM_001122607.1:c.476T>A
ENST00000300305.7:c.557T>A
ENST00000344691.8:c.476T>A
ENST00000358356.9:c.476T>A
ENST00000399237.6:c.521T>A
ENST00000399240.5:c.476T>A
ENST00000437180.5:c.557T>A
ENST00000467577.1:n.49T>A
ENST00000482318.5:c.*147T>A

Uncertain Significance

• Met criteria codes: PP3 PM2 PM1_Supporting

• Not Met criteria codes: PVS1 PS3 PS1 PS4 PP1 PM4 PM5 PM6 BA1 BS3 BS1 BS4 BP7 BP4 BP2

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The NM_001754.4:c.557T>A (p.Val186Asp) missense variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). It has a REVEL score >0.75 (0.953) (PP3). This variant affects one of the residues (AA 105-204) within the RHD (PM1_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: PM2, PP3, PM1_Supporting.

Met criteria codes

• PP3: REVEL: 0.953 >0.75
• PM2: The variant is absent from all population databases.
• PM1_Supporting: Residue in RUNT domain (105-204aa).

Not Met criteria codes

• PVS1: 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
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: IBMF, novel mutation, assumed skin fibroblast based on testing done at UofC.
• PP1: 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
• PM5: 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
• BA1: 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
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS4: 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
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2019-07-30

Published on: 2019-08-02