Variant: NM_001754.5(RUNX1):c.509-17C>T

CA2737742321

2874041 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 54fc0a59-ef78-4cc5-86f4-bd3bdf461765

Approved on: 2025-02-25

Published on: 2025-02-25

HGVS expressions

NM_001754.5:c.509-17C>T
NM_001754.5(RUNX1):c.509-17C>T
NC_000021.9:g.34859595G>A
CM000683.2:g.34859595G>A
NC_000021.8:g.36231892G>A
CM000683.1:g.36231892G>A
NC_000021.7:g.35153762G>A
NG_011402.2:g.1130117C>T
ENST00000675419.1:c.509-17C>T
ENST00000300305.7:c.509-17C>T
ENST00000344691.8:c.428-17C>T
ENST00000358356.9:c.428-17C>T
ENST00000399237.6:c.473-17C>T
ENST00000399240.5:c.428-17C>T
ENST00000437180.5:c.509-17C>T
ENST00000482318.5:c.*99-17C>T
NM_001001890.2:c.428-17C>T
NM_001122607.1:c.428-17C>T
NM_001754.4:c.509-17C>T
NM_001001890.3:c.428-17C>T
NM_001122607.2:c.428-17C>T

Likely Benign

• Met criteria codes: BP7 BP4 PM2_Supporting

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

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

NM_001754.5(RUNX1):c.509-17C>T is an intronic variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant has a SpliceAI score ≤ 0.20 (0) and evolutionary conservation algorithms predict the site are not available. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4, BP7.

Met criteria codes

• BP7: This variant has a SpliceAI score ≤ 0.20 (0) and evolutionary conservation algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (not available)) (BP7).
• BP4: This intronic variant has a SpliceAI score ≤ 0.20 (0) (BP4).
• PM2_Supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

Not Met criteria codes

• PVS1: This variant is not a null variant.
• BS2: not applicable
• BS4: Segregation data for this variant has not been reported in literature.
• BS3: In vitro or in vivo functional data has not been reported for this variant in the literature.
• BS1: This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.
• BP5: not applicable
• BP3: not applicable
• BP2: This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
• BP1: Not applicable
• PM5: This variant is not a missense variant.
• PM4: This variant is not an in-frame deletion/insertion.
• PM3: not applicable
• PM1: This variant is not a missense variant.
• PS1: This variant is not a missense variant.
• PS2: De novo data for this variant has not been reported in literature.
• PS4: Proband data for this variant has not been reported in literature.
• PS3: In vitro or in vivo functional data has not been reported for this variant in the literature.
• PM6: De novo data for this variant has not been reported in literature.
• PP4: not applicable
• PP1: Segregation data for this variant has not been reported in literature.
• PP3: This synonymous or intronic variant does not have a REVEL score ≥ 0.88 or a SpliceAI score ≥ 0.38.
• PP2: Not applicable
• BA1: This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.