Variant: NM_001754.5(RUNX1):c.1099G>C (p.Gly367Arg)

Version: 1.0
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CA410148133

2126320 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 7279e349-fac0-40be-9caf-43641b65ce38

Approved on: 2024-08-01

Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.1099G>C
NM_001754.5(RUNX1):c.1099G>C (p.Gly367Arg)
NC_000021.9:g.34792479C>G
CM000683.2:g.34792479C>G
NC_000021.8:g.36164776C>G
CM000683.1:g.36164776C>G
NC_000021.7:g.35086646C>G
NG_011402.2:g.1197233G>C
ENST00000675419.1:c.1099G>C
ENST00000300305.7:c.1099G>C
ENST00000344691.8:c.1018G>C
ENST00000399240.5:c.826G>C
ENST00000437180.5:c.1099G>C
ENST00000482318.5:c.*689G>C
NM_001001890.2:c.1018G>C
NM_001754.4:c.1099G>C
NM_001001890.3:c.1018G>C

Uncertain Significance

• Met criteria codes: PM2_Supporting

• Not Met criteria codes: PS2 PS4 PS3 PS1 PP1 PP3 PM6 PM1 PM4 PM5 PVS1 BA1 BS4 BS3 BS1 BP7 BP2 BP4

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.1099G>C (p.Gly367Arg) 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 of 0.707, which does not allow applying either PP3 (>0.88) or BP4 (<0.50). 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: 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).

Not Met criteria codes

• 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 (0.707).
• 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 367, 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.
• BA1: This rule cannot be applied since the variant is completely absent from all population databases.
• 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.
• BP4: This rule cannot be applied since this missense variant has not a REVEL score <0.50 (0.707).