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]

Variant: NM_001754.4(RUNX1):c.579C>T (p.Ile193=)

CA320617998

532685 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7bacc9f5-a27a-4ce4-82d3-b6aebf7205f8
Approved on: 2022-07-07
Published on: 2022-07-07

HGVS expressions

NM_001754.4:c.579C>T
NM_001754.4(RUNX1):c.579C>T (p.Ile193=)
NC_000021.9:g.34859508G>A
CM000683.2:g.34859508G>A
NC_000021.8:g.36231805G>A
CM000683.1:g.36231805G>A
NC_000021.7:g.35153675G>A
NG_011402.2:g.1130204C>T
ENST00000675419.1:c.579C>T
ENST00000300305.7:c.579C>T
ENST00000344691.8:c.498C>T
ENST00000358356.9:c.498C>T
ENST00000399237.6:c.543C>T
ENST00000399240.5:c.498C>T
ENST00000437180.5:c.579C>T
ENST00000467577.1:n.71C>T
ENST00000482318.5:c.*169C>T
NM_001001890.2:c.498C>T
NM_001122607.1:c.498C>T
NM_001001890.3:c.498C>T
NM_001122607.2:c.498C>T
NM_001754.5:c.579C>T
NM_001754.5(RUNX1):c.579C>T (p.Ile193=)
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Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 25
PS3 PS2 PS4 PS1 PP1 PP4 PP3 PP2 PM3 PM4 PM5 PM1 PM6 PM2 PVS1 BA1 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP1

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
Although this c.579C>T (p.Ile193=) synonymous variant is not predicted to have any splicing impact per SpliceAI (BP4), it is located at a highly conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP score = 4.63809 in GRCh38) and only present once in gnomAD v3. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4.
Met criteria codes
BP4
SpliceAI doesn't predict a significant splicing impact (Δ scores ≤ 0.20).
Not Met criteria codes
PS3
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
Literature not found in HGMD, Google/Google Scholar searches, or COSMIC.
PS1
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
PP4
Not applicable
PP3
SpliceAI doesn't predict a significant splicing impact (Δ scores ≤ 0.20).
PP2
Not applicable
PM3
Not applicable
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
PM1
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
PM2
gnomAD v2: absent with ≥20x coverage gnomAD v3: ALL: 0.0006571% (1/152180) - NFE: 0.001470% (1/68036)
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
MAF < 0.15% gnomAD v2: absent with ≥20x coverage gnomAD v3: ALL: 0.0006571% (1/152180) - NFE: 0.001470% (1/68036)
BS2
Not applicable
BS4
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
MAF < 0.015% gnomAD v2: absent with ≥20x coverage gnomAD v3: ALL: 0.0006571% (1/152180) - NFE: 0.001470% (1/68036)
BP5
Not applicable
BP7
Synonymous variant located at a highly conserved nucleotide (PhyloP = 4.63809 in GRCh38), and the variant is not the reference nucleotide in one primate and/or 3 mammals. SpliceAI doesn't predict any splicing impact.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
Not applicable
BP1
Not applicable
Curation History
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