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]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document

Variant: NM_001122607.2:c.408T>A

CA410202503

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c0e61fb7-cd6b-470c-a216-d9d4f758f503

HGVS expressions

NM_001122607.2:c.408T>A
NC_000021.9:g.34880576A>T
CM000683.2:g.34880576A>T
NC_000021.8:g.36252873A>T
CM000683.1:g.36252873A>T
NC_000021.7:g.35174743A>T
NG_011402.2:g.1109136T>A
ENST00000675419.1:c.489T>A
ENST00000300305.7:c.489T>A
ENST00000344691.8:c.408T>A
ENST00000358356.9:c.408T>A
ENST00000399237.6:c.453T>A
ENST00000399240.5:c.408T>A
ENST00000437180.5:c.489T>A
ENST00000482318.5:c.*79T>A
NM_001001890.2:c.408T>A
NM_001122607.1:c.408T>A
NM_001754.4:c.489T>A
NM_001001890.3:c.408T>A
NM_001754.5:c.489T>A

Uncertain Significance

Met criteria codes 3
PM2_Supporting PM1_Supporting PP3
Not Met criteria codes 23
PM6 PM3 PM4 PM5 PVS1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS3 PS1 PS4 BA1 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
The c.489T>A (p.Phe163Leu) variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant has a REVEL score of ≥0.88 (0.914) (PP3). The variant occurs at residue 163 located in the RHD, which is determined to be a critical functional domain by MM-VCEP (PM1_Supporting). The variant has not been reported in the germ line of patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge. 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
Phe163Leu is absent from gnomAD v2 and v3 at >20x coverage
PM1_Supporting
The variant occurs at residue 163 located in the RHD, which is determined to be a critical functional domain by MM-VCEP, meeting PM1_Supporting.
PP3
Variant meets PP3 with REVEL score of 0.914 (threshold: >0.75)
Not Met criteria codes
PM6
No data currently available
PM3
MM-VCEP deemed N/A for RUNX1
PM4
N/A
PM5
Phe163Cys variant at the same residue is provisionally classified as VUS by MM-VCEP. PM5 not applicable
PVS1
N/A
BS2
MM-VCEP deemed N/A for RUNX1
BS4
No data currently available
BS3
No data currently available
BS1
Variant meets PM2
BP2
No data currently available
BP3
MM-VCEP deemed N/A for RUNX1
BP4
Variant meets PP3
BP1
MM-VCEP deemed N/A for RUNX1
BP5
MM-VCEP deemed N/A for RUNX1
BP7
N/A
PS2
No data currently available
PS3
No data currently available
PS1
N/A
PS4
The variant has not been reported in the germ line of patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge.
BA1
Variant meets PM2
PP4
MM-VCEP deemed N/A for RUNX1
PP1
No data currently available
PP2
MM-VCEP deemed N/A for RUNX1
Approved on: 2022-07-08
Published on: 2022-07-08
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