Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • See Evidence submitted by expert panel for details.

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
Link to MONDO
UUID: 3ff9a59f-f463-4e1a-942e-a60afc15686a
Approved on: 2019-07-30
Published on: 2019-08-02

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 3
PP3 PM2 PM1_Supporting
Not Met criteria codes 15
BA1 PS3 PS1 PS4 PP1 PM6 PM4 PM5 BS3 BS1 BS4 BP7 BP4 BP2 PVS1

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
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
BA1
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.
IBMF, novel mutation, assumed skin fibroblast based on testing done at UofC PubMed:28104920
PP1
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
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
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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