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

UUID: 1d2ff086-abdf-4f5e-8985-3cebc995a9d7

Approved on: 2023-11-13

Published on: 2023-11-13

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: BP7 BP4

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

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

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

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
• PVS1: 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
• 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.
• 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
• 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