The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


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

CA248819

212089 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 3ff9a59f-f463-4e1a-942e-a60afc15686a
Approved on: 2025-01-15
Published on: 2025-01-15

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
ENST00000675419.1:c.557T>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
NM_001001890.2:c.476T>A
NM_001122607.1:c.476T>A
NM_001001890.3:c.476T>A
NM_001122607.2:c.476T>A
NM_001754.5:c.557T>A
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Uncertain Significance

Met criteria codes 3
PM2_Supporting PM1_Supporting PP3
Not Met criteria codes 23
PM6 PM3 PM5 PM4 BA1 BS2 PVS1 BS4 BS1 BS3 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS4 PS1 PS3 PP4 PP1 PP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.4(RUNX1):c.557T>A (p.Val186Asp) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). It has a REVEL score of 0.953 (> 0.75), supporting PP3. This variant is located within the Runt Homology Domain (RHD), affecting one of the residues (AA 105-204) but not an established hotspot residue (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_supporting, PP3, PM1_supporting.
Met criteria codes
PM2_Supporting
The variant is absent from all population databases.
PM1_Supporting
Residue in RUNT domain (105-204aa).
PP3
REVEL: 0.953 >0.75
Not Met criteria codes
PM6
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
BA1
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
PVS1
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
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
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
BP2
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
BP4
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
PS2
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.
PS1
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
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
Curation History
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