Variant: NM_001754.5(RUNX1):c.968C>G (p.Thr323Arg)

CA320251671

2076125 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 735a8cdc-ae26-4fbf-b706-49da306cefca

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.968C>G
NM_001754.5(RUNX1):c.968C>G (p.Thr323Arg)
NC_000021.9:g.34792610G>C
CM000683.2:g.34792610G>C
NC_000021.8:g.36164907G>C
CM000683.1:g.36164907G>C
NC_000021.7:g.35086777G>C
NG_011402.2:g.1197102C>G
ENST00000675419.1:c.968C>G
ENST00000300305.7:c.968C>G
ENST00000344691.8:c.887C>G
ENST00000399240.5:c.695C>G
ENST00000437180.5:c.968C>G
ENST00000482318.5:c.*558C>G
NM_001001890.2:c.887C>G
NM_001754.4:c.968C>G
NM_001001890.3:c.887C>G

Uncertain Significance

• Met criteria codes: PM2_Supporting BP4

• Not Met criteria codes: BS2 BS4 BS3 BS1 PVS1 BP7 BP5 BP2 BP3 BP1 PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 BA1 PM5 PM1 PM3 PM4 PM6

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.968C>G (p.Thr323Arg) is a missense variant. This variant is absent from both gnomAD v2.1 and gnomAD v3.1.2 (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 <0.50 (0.055) (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

• PM2_Supporting: This variant is absent from both gnomAD v2.1 and gnomAD v3.1.2
• BP4: This missense variant has a REVEL score <0.50 (0.055)

Not Met criteria codes

• BS2: This rule is not applicable for MM-VCEP
• BS4: No case study found
• BS3: No functional studies found
• BS1: This variant is absent from both gnomAD v2.1 and gnomAD v3.1.2
• PVS1: This is not a null variant
• BP7: This is not a synonymous variant
• BP5: This rule is not applicable for MM-VCEP
• BP2: No case study found
• BP3: This rule is not applicable for MM-VCEP
• BP1: This rule is not applicable for MM-VCEP
• PS4: No proband meeting RUNX1 phenotypic criteria has been observed
• PS2: No case study found
• PS1: A missense change in amino acid 323 has not been determined to be pathogenic before
• PS3: No functional studies found
• PP1: No case study found
• PP4: This rule is not applicable for MM-VCEP
• PP3: BP4 Met
• PP2: This rule is not applicable for MM-VCEP
• BA1: This variant is absent from both gnomAD v2.1 and gnomAD v3.1.2
• PM5: A missense change in amino acid 323 has not been determined to be pathogenic before
• PM1: The variant is located outside of the mutational hot spot and/or critical and well- established functional domain as defined by the MM-VCEP (AA 89-204)
• PM3: This rule is not applicable for MM-VCEP
• PM4: This is a missense variant
• PM6: No case study found