Variant: NM_001754.5(RUNX1):c.101C>G (p.Ala34Gly)

CA410204316

2663436 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: aa41b89c-79a9-41ef-9413-63225fdf1dde

Approved on: 2024-10-29

Published on: 2024-10-29

HGVS expressions

NM_001754.5:c.101C>G
NM_001754.5(RUNX1):c.101C>G (p.Ala34Gly)
NC_000021.9:g.34887093G>C
CM000683.2:g.34887093G>C
NC_000021.8:g.36259390G>C
CM000683.1:g.36259390G>C
NC_000021.7:g.35181260G>C
NG_011402.2:g.1102619C>G
ENST00000675419.1:c.101C>G
ENST00000300305.7:c.101C>G
ENST00000344691.8:c.20C>G
ENST00000358356.9:c.20C>G
ENST00000399237.6:c.65C>G
ENST00000399240.5:c.20C>G
ENST00000437180.5:c.101C>G
ENST00000455571.5:c.62C>G
ENST00000475045.6:c.101C>G
ENST00000482318.5:c.59-6380C>G
NM_001001890.2:c.20C>G
NM_001122607.1:c.20C>G
NM_001754.4:c.101C>G
NM_001001890.3:c.20C>G
NM_001122607.2:c.20C>G

Uncertain Significance

• Met criteria codes: BP4 PM2_Supporting

• Not Met criteria codes: BP2 BP3 BP1 BP7 BP5 PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 PM5 PM1 PM3 PM4 PM6 BA1 BS2 PVS1 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.101C>G (p.Ala34Gly) is a missense variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant has not been reported in any proband meeting at least one of the RUNX1-phenotypic criteria. This missense variant has a REVEL score <0.5 (0.407)(BP4). In summary, this variant meets the criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM2_supporting

Met criteria codes

• BP4: REVEL score is 0.407 ( BP4 ≤ 0.50 )
• PM2_Supporting: This variant is completely absent from all population databases (gnomAD v2.1.1, v3.1.2, and v4.0.0) with at least 20x coverage for RUNX1 (PM2_supporting).

Not Met criteria codes

• BP2: No case studies found
• BP3: This rule is not applicable for MM-VCEP
• BP1: This rule is not applicable for MM-VCEP
• BP7: This is a missense variant
• BP5: This rule is not applicable for MM-VCEP
• PS4: No case-studies found meeting FPD-MM phenotypic criteria
• PS2: No case study found
• PS1: Amino acid 34 has not previously been determined as pathogenic
• PS3: No assays found
• PP1: No case studies found
• PP4: This rule is not applicable for MM-VCEP
• PP3: BP4 Met
• PP2: This rule is not applicable for MM-VCEP
• PM5: A missense change in amino acid 34 has not previously been determined as pathogenic
• PM1: Amino acid 34 is not in a mutational hot spot or functional domain
• PM3: This rule is not applicable for MM-VCEP
• PM4: This is a missense variant
• PM6: No case study found
• BA1: PM2_supporting met
• BS2: This rule is not applicable for MM-VCEP
• PVS1: This is a missense variant
• BS4: No case studies found
• BS3: No assays found
• BS1: PM2_supporting met