Variant: NM_001754.5(RUNX1):c.339del (p.Ile114fs)

CA658824421

561235 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: aa00bb05-fdbd-48e3-b409-3cdd4e1692c1

Approved on: 2022-07-05

Published on: 2022-07-05

HGVS expressions

NM_001754.5:c.339del
NM_001754.5(RUNX1):c.339del (p.Ile114fs)
NC_000021.9:g.34886857del
CM000683.2:g.34886857del
NC_000021.8:g.36259154del
CM000683.1:g.36259154del
NC_000021.7:g.35181024del
NG_011402.2:g.1102857del
ENST00000675419.1:c.339del
ENST00000300305.7:c.339del
ENST00000344691.8:c.258del
ENST00000358356.9:c.258del
ENST00000399237.6:c.303del
ENST00000399240.5:c.258del
ENST00000437180.5:c.339del
ENST00000455571.5:c.300del
ENST00000482318.5:c.59-6142del
NM_001001890.2:c.258del
NM_001122607.1:c.258del
NM_001754.4:c.339del
NM_001001890.3:c.258del
NM_001122607.2:c.258del

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

• Met criteria codes: PM2_Supporting PVS1

• Not Met criteria codes: PM6 PM5 PM1 PM3 PM4 BS2 BS4 BS3 BS1 BP7 BP5 BP2 BP3 BP4 BP1 PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 BA1

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.339del (p.Ile114fs) is a frameshift variant predicted to undergo NMD (PVS1 SNV tree). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1 and PM2_supporting

Met criteria codes

• PM2_Supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).
• PVS1: NM_001754.5(RUNX1):c.339del (p.Ile114fs) is a frameshift variant predicted to undergo NMD (PVS1 SNV tree)

Not Met criteria codes

• PM6: No case studies found
• PM5: Amino acid has not been previously established as pathogenic
• PM1: Not a missense variant
• PM3: This rule is not applicable for MM-VCEP
• PM4: This is not an in-frame deletion/insertion that affects at least one of the other residues (AA 89-204) within the RHD
• BS2: This rule is not applicable for MM-VCEP
• BS4: No case studies found
• BS3: No functional studies found
• BS1: This variant is completely absent from all population databases with at least 20x coverage for RUNX1
• BP7: Not applicable, not a synonymous or intronic variant
• BP5: This rule is not applicable for MM-VCEP
• BP2: Variant not present in gnomAD v2.1.1 or v3.1.2
• BP3: This rule is not applicable for MM-VCEP
• BP4: Not a missense, synonymous, or intronic variant therefore code does not apply
• BP1: This rule is not applicable for MM-VCEP
• PS4: No case studies found
• PS2: No case studies found
• PS1: Amino acid has not been previously established as pathogenic
• PS3: No functional studies found
• PP1: No case studies found
• PP4: This rule is not applicable for MM-VCEP
• PP3: Not a missense, synonymous, or intronic variant therefore code does not apply
• PP2: This rule is not applicable for MM-VCEP
• BA1: This variant is completely absent from all population databases with at least 20x coverage for RUNX1