Variant: NM_001754.5(RUNX1):c.999G>T (p.Pro333=)

Version: 1.0
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CA320251631

1628628 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Inheritance Mode: Autosomal dominant inheritance

UUID: cf7937f9-436e-4311-8e81-832624ace4fc

Approved on: 2024-06-24

Published on: 2024-06-24

HGVS expressions

NM_001754.5:c.999G>T
NM_001754.5(RUNX1):c.999G>T (p.Pro333=)
NC_000021.9:g.34792579C>A
CM000683.2:g.34792579C>A
NC_000021.8:g.36164876C>A
CM000683.1:g.36164876C>A
NC_000021.7:g.35086746C>A
NG_011402.2:g.1197133G>T
ENST00000675419.1:c.999G>T
ENST00000300305.7:c.999G>T
ENST00000344691.8:c.918G>T
ENST00000399240.5:c.726G>T
ENST00000437180.5:c.999G>T
ENST00000482318.5:c.*589G>T
NM_001001890.2:c.918G>T
NM_001754.4:c.999G>T
NM_001001890.3:c.918G>T

Likely Benign

• Met criteria codes: PM2_Supporting BP4 BP7

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

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

This synonymous variant has a SpliceAI Δ score of 0.00 (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.008 (< 2)) (BP7). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). 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: BP4, BP7, PM2_supporting.

Met criteria codes

• PM2_Supporting: 0 alleles gnomAD V2, 0 alleles gnomAD V3 This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).
• BP4: SpliceAI Δ score 0.00 PhyloP score: -0.093 BP4: This synonymous variant has a SpliceAI Δ score < 0.20 PhyloP score < 2
• BP7: SpliceAI Δ score 0.00 PhyloP score: -0.093 BP7: Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.093) (BP7).

Not Met criteria codes

• PVS1: not applicable
• PS2: nil data
• PS4: nil data
• PS3: nil data
• PS1: not applicable
• PP4: nil data
• PP1: nil data
• PP3: BP4 met
• PP2: not applicable
• PM3: not applicable
• PM1: not applicable
• PM4: not applicable
• PM5: not applicable
• PM6: nil data
• BS2: not applicable
• BS4: nil data
• BS3: nil data
• BP2: not applicable
• BP3: not applicable
• BP1: not applicable
• BP5: not applicable