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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  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001754.5(RUNX1):c.557T>G (p.Val186Gly)

CA410208053

2116304 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ca601e9a-2b21-49cb-bbe6-1453754c0f60
Approved on: 2024-08-01
Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.557T>G
NM_001754.5(RUNX1):c.557T>G (p.Val186Gly)
NC_000021.9:g.34859530A>C
CM000683.2:g.34859530A>C
NC_000021.8:g.36231827A>C
CM000683.1:g.36231827A>C
NC_000021.7:g.35153697A>C
NG_011402.2:g.1130182T>G
ENST00000675419.1:c.557T>G
ENST00000300305.7:c.557T>G
ENST00000344691.8:c.476T>G
ENST00000358356.9:c.476T>G
ENST00000399237.6:c.521T>G
ENST00000399240.5:c.476T>G
ENST00000437180.5:c.557T>G
ENST00000467577.1:n.49T>G
ENST00000482318.5:c.*147T>G
NM_001001890.2:c.476T>G
NM_001122607.1:c.476T>G
NM_001754.4:c.557T>G
NM_001001890.3:c.476T>G
NM_001122607.2:c.476T>G

Uncertain Significance

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

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_001754.5(RUNX1):c.557T>G (p.Val186Gly)is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This missense variant is located within the Runt Homology Domain (AA 89-204), but does not occur in an established hotspot residue (PM1_supporting). This variant has a REVEL score ≥ 0.88 (0.957) (PP3). 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, PM1_supporting, PP3.
Met criteria codes
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting).
PP3
This missense variant has a REVEL score ≥ (0.88) (0.957). (PP3)
PM1_Supporting
This variant affects an amino acid residue within the RHD domain that is defined as a mutational hotspot by the ClinGen MM-VCEP (PM1_Supporting).
Not Met criteria codes
PVS1
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
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
This rule is not applicable to the MMVCEP.
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
To our knowledge, this variant was not evaluated in transactivation assays.
BS1
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
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
This rule is not applicable to the MMVCEP.
PM3
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Clinvar has one entry (Invitae) for this variant but the affected status is unknown (Variation ID 2116304). To our knowledge, no publication has reported this information/variant to date.
PS3
To our knowledge, this variant was not evaluated in transactivation assays.
PS1
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
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