Variant: NM_001754.5(RUNX1):c.384T>C (p.Thr128=)

CA512318767

1667672 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 1c74237e-7f11-4726-87f7-33474ab97bae

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.384T>C
NM_001754.5(RUNX1):c.384T>C (p.Thr128=)
NC_000021.9:g.34880681A>G
CM000683.2:g.34880681A>G
NC_000021.8:g.36252978A>G
CM000683.1:g.36252978A>G
NC_000021.7:g.35174848A>G
NG_011402.2:g.1109031T>C
ENST00000675419.1:c.384T>C
ENST00000300305.7:c.384T>C
ENST00000344691.8:c.303T>C
ENST00000358356.9:c.303T>C
ENST00000399237.6:c.348T>C
ENST00000399240.5:c.303T>C
ENST00000437180.5:c.384T>C
ENST00000455571.5:c.345T>C
ENST00000482318.5:c.91T>C
NM_001001890.2:c.303T>C
NM_001122607.1:c.303T>C
NM_001754.4:c.384T>C
NM_001001890.3:c.303T>C
NM_001122607.2:c.303T>C

Likely Benign

• Met criteria codes: BP7 BP4 PM2_Supporting

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

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.384T>C (p.Thr128=) is a synonymous variant which has a SpliceAI score ≤ 0.20 (0.01) (BP4). This variant has a SpliceAI score ≤ 0.20 (0.01) and evolutionary conservation algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-0.77)) (BP7). 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 benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, PM2_supporting.

Met criteria codes

• BP7: This variant has a SpliceAI score ≤ 0.20 (0.01) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-0.77)) (BP7).
• BP4: This synonymous variant has a SpliceAI score ≤ 0.20 (0.01) (BP4).
• 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 does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
• PP1: Segregation data for this variant has not been reported in literature.
• PP4: This rule is not applicable for MM-VCEP.
• PP3: This synonymous or intronic variant does not have a REVEL score ≥ 0.88 or a SpliceAI score ≥ 0.38.
• PP2: This rule is not applicable for MM-VCEP.
• PM6: De novo data for this variant has not been reported in literature.
• PM5: This variant is not a missense variant.
• PM3: This rule is not applicable for MM-VCEP.
• PM4: This variant is not an in-frame deletion/insertion.
• PVS1: This variant is not a null variant.
• BS4: Segregation data for this variant has not been reported in literature.
• BS3: In vitro or in vivo functional data has not been reported for this variant in the literature.
• BS1: This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.
• BS2: This rule is not applicable for MM-VCEP.
• BP5: This rule is not applicable for MM-VCEP.
• BP2: This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
• BP3: This rule is not applicable for MM-VCEP.
• BP1: This rule is not applicable for MM-VCEP.
• PS2: De novo data for this variant has not been reported in literature.
• PS4: Proband data for this variant has not been reported in literature.
• PS3: In vitro or in vivo functional data has not been reported for this variant in the literature.
• PS1: This variant is not a missense variant.