Variant: NM_001754.5(RUNX1):c.730G>A (p.Ala244Thr)

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CA410206807

972242 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 59ae24de-bc4e-421f-967e-c70fd34bea09

Approved on: 2024-10-29

Published on: 2024-10-29

HGVS expressions

NM_001754.5:c.730G>A
NM_001754.5(RUNX1):c.730G>A (p.Ala244Thr)
NC_000021.9:g.34834485C>T
CM000683.2:g.34834485C>T
NC_000021.8:g.36206782C>T
CM000683.1:g.36206782C>T
NC_000021.7:g.35128652C>T
NG_011402.2:g.1155227G>A
ENST00000675419.1:c.730G>A
ENST00000300305.7:c.730G>A
ENST00000344691.8:c.649G>A
ENST00000358356.9:c.649G>A
ENST00000399237.6:c.694G>A
ENST00000399240.5:c.532+24989G>A
ENST00000437180.5:c.730G>A
ENST00000469087.1:n.266G>A
ENST00000482318.5:c.*320G>A
NM_001001890.2:c.649G>A
NM_001122607.1:c.649G>A
NM_001754.4:c.730G>A
NM_001001890.3:c.649G>A
NM_001122607.2:c.649G>A

Uncertain Significance

• Met criteria codes: PM2_Supporting BP4

• Not Met criteria codes: PP1 PP4 PM3 PM5 PS3 PS1 PVS1 BA1 BP2 BS4 BS3 BS1

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.730G>A (p.Ala244Thr) is a missense variant which has a REVEL score < 0.50 (0.277) and a SpliceAI score ≤ 0.20 (0.08) (BP4). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM2_supporting.

Met criteria codes

• PM2_Supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).
• BP4: This variant has a REVEL score < 0.50 (0.277) and a SpliceAI score ≤ 0.20 (0.08) (BP4).

Not Met criteria codes

• PP1: Segregation data for this variant has not been reported in literature.
• PP4: This rule is not applicable for MM-VCEP.
• PM3: This rule is not applicable for MM-VCEP.
• PM5: There has not yet been a different missense change determined to be pathogenic at this amino acid residue.
• PS3: In vitro or in vivo functional data has not been reported for this variant in the literature.
• PS1: There has not yet been a missense change determined to be pathogenic at this amino acid residue.
• PVS1: This variant is not a null variant.
• BA1: This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
• 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.
• 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.