Variant: NM_001754.5(RUNX1):c.270G>A (p.Val90=)

CA512318868

1116571 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 142360ab-0f52-479d-abb9-f98ecafaa7aa

Approved on: 2024-09-11

Published on: 2024-09-11

HGVS expressions

NM_001754.5:c.270G>A
NM_001754.5(RUNX1):c.270G>A (p.Val90=)
NC_000021.9:g.34886924C>T
CM000683.2:g.34886924C>T
NC_000021.8:g.36259221C>T
CM000683.1:g.36259221C>T
NC_000021.7:g.35181091C>T
NG_011402.2:g.1102788G>A
ENST00000675419.1:c.270G>A
ENST00000300305.7:c.270G>A
ENST00000344691.8:c.189G>A
ENST00000358356.9:c.189G>A
ENST00000399237.6:c.234G>A
ENST00000399240.5:c.189G>A
ENST00000437180.5:c.270G>A
ENST00000455571.5:c.231G>A
ENST00000482318.5:c.59-6211G>A
NM_001001890.2:c.189G>A
NM_001122607.1:c.189G>A
NM_001754.4:c.270G>A
NM_001001890.3:c.189G>A
NM_001122607.2:c.189G>A

Uncertain Significance

• Met criteria codes: PM2_Supporting

• Not Met criteria codes: BA1 PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 PM6 PM5 PM1 PM3 PM4 BS2 BS4 BS3 BS1 BP7 BP5 BP2 BP3 BP4 BP1 PVS1

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.270G>A (p.Val90=) is a synonymous variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). 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 with at least 20x coverage for RUNX1 (PM2_supporting).

Not Met criteria codes

• BA1: This variant is completely absent from all population databases with at least 20x coverage for RUNX1
• PS4: prevalence of variant is not significantly increased compared to prevalence in controls
• PS2: no case studies found
• PS1: Amino acid location has not been previously established as pathogenic
• PS3: No functional studies found
• PP1: no case studies found
• PP4: This rule is not applicable for the MM-VCEP
• PP3: Synonymous variant therefore no REVEL score applicable and SpliceAI is not ≥0.38 (0.26 Donor Gain)
• PP2: This rule is not applicable for the MM-VCEP
• PM6: No case studies found
• PM5: Not a missense variant
• PM1: Not a missense variant
• PM3: This rule is not applicable for the MM-VCEP
• PM4: Not an in-frame deletion/insertion
• BS2: This rule is not applicable for the 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: SpliceAI score <0.20.
• BP5: This rule is not applicable for the MM-VCEP
• BP2: Variant absent in gnomAD therefore no homozygotes present
• BP3: This rule is not applicable for the MM-VCEP
• BP4: Synonymous variant therefore no REVEL score applicable and SpliceAI is not ≤0.20 (0.26 Donor Gain)
• BP1: This rule is not applicable for the MM-VCEP
• PVS1: Not a null variant