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

Variant: NM_001754.5(RUNX1):c.291C>T (p.Phe97=)

CA512318853

1088304 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1d2ff086-abdf-4f5e-8985-3cebc995a9d7

HGVS expressions

NM_001754.5:c.291C>T
NM_001754.5(RUNX1):c.291C>T (p.Phe97=)
NC_000021.9:g.34886903G>A
CM000683.2:g.34886903G>A
NC_000021.8:g.36259200G>A
CM000683.1:g.36259200G>A
NC_000021.7:g.35181070G>A
NG_011402.2:g.1102809C>T
ENST00000675419.1:c.291C>T
ENST00000300305.7:c.291C>T
ENST00000344691.8:c.210C>T
ENST00000358356.9:c.210C>T
ENST00000399237.6:c.255C>T
ENST00000399240.5:c.210C>T
ENST00000437180.5:c.291C>T
ENST00000455571.5:c.252C>T
ENST00000482318.5:c.59-6190C>T
NM_001001890.2:c.210C>T
NM_001122607.1:c.210C>T
NM_001754.4:c.291C>T
NM_001001890.3:c.210C>T
NM_001122607.2:c.210C>T

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 24
PS2 PS4 PS3 PS1 PP1 PP4 PP3 PP2 PVS1 BA1 BS4 BS3 BS1 BS2 PM1 PM5 PM3 PM4 PM6 PM2 BP5 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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.5(RUNX1):c.291C>T (p.Phe97=) variant is reported at a MAF of 0.00005 (0.005%, 1/21626 alleles) in the non-Finnish European subpopulation of the gnomAD v2.1.1 cohort, and does not meet thresholds for BA1, BS1, or PM2. The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge. REVEL score is not calculable for a synonymous variant; SpiceAI predicts: Acceptor loss 0.02, Donor loss 0.00, Acceptor gain 0.00, Donor gain 0.00. Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.74248< 2.0) In summary, the clinical significance of this variant is likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.
Met criteria codes
BP7
Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.74248< 2.0) (BP7).
BP4
REVEL score is not calculable for a synonymous variant; SpiceAI predicts: Acceptor loss 0.02, Donor loss 0.00, Acceptor gain 0.00, Donor gain 0.00. (BP4)
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No literature available for this variant
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
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
This rule is not applicable for MM-VCEP
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
This rule is not applicable for MM-VCEP
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No literature found for this variant.
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
This rule is not applicable for MM-VCEP
PM1
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
PM3
This rule is not applicable for MM-VCEP
PM4
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
This variant is present at an allele frequency of 0.00005 (0.005%, 1/21626 alleles) in gnomAD version 2. This does not meet criteria for BA1, BS1, or PM2.
BP5
This rule is not applicable for MM-VCEP
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
This rule is not applicable for MM-VCEP
BP1
This rule is not applicable for MM-VCEP
Approved on: 2023-11-13
Published on: 2023-11-13
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