Variant: NM_001754.5(RUNX1):c.1098C>G (p.Ile366Met)

CA410148136

2002610 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 9333ccc2-ef4c-4ea0-a80d-cca0fc543ae4

Approved on: 2024-08-01

Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.1098C>G
NM_001754.5(RUNX1):c.1098C>G (p.Ile366Met)
NC_000021.9:g.34792480G>C
CM000683.2:g.34792480G>C
NC_000021.8:g.36164777G>C
CM000683.1:g.36164777G>C
NC_000021.7:g.35086647G>C
NG_011402.2:g.1197232C>G
ENST00000675419.1:c.1098C>G
ENST00000300305.7:c.1098C>G
ENST00000344691.8:c.1017C>G
ENST00000399240.5:c.825C>G
ENST00000437180.5:c.1098C>G
ENST00000482318.5:c.*688C>G
NM_001001890.2:c.1017C>G
NM_001754.4:c.1098C>G
NM_001001890.3:c.1017C>G

Uncertain Significance

• Met criteria codes: PM2_Supporting BP4

• Not Met criteria codes: PM6 PM1 PM4 PM5 PVS1 BS4 BS3 BS1 BP7 BP2 PS2 PS4 PS3 PS1 PP1 PP3 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.1098C>G (p.Ile366Met) is a missense variant which is completely absent from all population databases (gnomAD v2.1.1 and v3.1.2) with at least 20x coverage for RUNX1 (PM2_supporting). It has a REVEL score <0.50 (0.451) (BP4). Additionally, there is no previous report of this variant. 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 (gnomAD v2.1.1 and v3.1.2) with at least 20x coverage for RUNX1 (PM2_supporting).
• BP4: This missense variant has a REVEL score <0.50 (0.451).

Not Met criteria codes

• PM6: This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.
• PM1: This rule cannot be applied since this missense variant affects amino acid residue 366, which is out of RHD or residues 89-204.
• PM4: This rule cannot be applied since this is a missense variant.
• PM5: This rule cannot be applied because, to our knowledge, this missense variant does not impact an amino acid residue where a different pathogenic missense change has previously been observed.
• PVS1: This rule cannot be applied since this is a missense variant.
• BS4: This rule cannot be applied since, to our knowledge, this variant has not been reported in any study and we have no information about segregation.
• BS3: To our knowledge, no in vitro or in vivo functional studies are available for this variant.
• BS1: This rule cannot be applied since the variant is completely absent from all population databases.
• BP7: This rule cannot be applied since this is a missense variant.
• BP2: This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.
• PS2: This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.
• PS4: This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.
• PS3: To our knowledge, no in vitro or in vivo functional studies are available for this variant.
• PS1: This rule cannot be applied because, to our knowledge, this missense variant does not generate the same amino acid change as a previously identified pathogenic variant regardless of nucleotide change.
• PP1: This rule cannot be applied since, to our knowledge, this variant has not been reported in any study and we have no information about its cosegregation with the disease.
• PP3: This rule cannot be applied since this missense variant has not a REVEL score >0.88 (0.451).
• BA1: This rule cannot be applied since the variant is completely absent from all population databases.