Variant: NM_001754.5(RUNX1):c.*3277G>T

CA10644615

339812 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 9f6dc474-f13c-4794-bb99-19dd69c52cc8

Approved on: 2023-11-13

Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.*3277G>T
NM_001754.5(RUNX1):c.*3277G>T
NC_000021.9:g.34788858C>A
CM000683.2:g.34788858C>A
NC_000021.8:g.36161155C>A
CM000683.1:g.36161155C>A
NC_000021.7:g.35083025C>A
NG_011402.2:g.1200854G>T
ENST00000675419.1:c.*3277G>T
ENST00000300305.7:c.*3277G>T
ENST00000344691.8:c.*3277G>T
ENST00000437180.5:c.*3277G>T
NM_001001890.2:c.*3277G>T
NM_001754.4:c.*3277G>T
NM_001001890.3:c.*3277G>T

Likely Benign

• Met criteria codes: BP4 PM2_Supporting

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

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.*3277G>T is an intronic variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). REVEL score is not applicable and SPliceAI is ≤0.20 (0.01) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.68 < 2.0) (BP7). In summary, the clinical significance of this variant is 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

• BP4: This 3'UTR variant has a SpliceAI score ≤ 0.20 (Acceptor Loss 0.01).
• PM2_Supporting: Variant is not present in population databases (gnomAD v2.1 or v3.1.2)

Not Met criteria codes

• PVS1: This variant is not a null variant, not impacting any of the following processes or sites: Nonsense, frameshift, canonical +/- 1 or 2 splice sites, initiation codon, single exon deletion, multiple exon deletions
• BA1: Variant is not present in population databases (gnomAD v2.1 or v3.1.2)
• BP5: This rule is not applicable for MM-VCEP
• BP2: This variant has not been detected in a homozygous state in an individual or in a population database (gnomAD). 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
• BS4: This variant has not been reported in probands.
• BS3: This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.
• BS1: Variant is not present in population databases (gnomAD v2.1 or v3.1.2)
• BS2: This rule is not applicable for MM-VCEP
• PP1: This variant was not found to co-segregate with disease in multiple affected family members.
• PP4: This rule is not applicable for MM-VCEP
• PP3: This intronic variant does not have a SpliceAI score of ≥ 0.38 (Acceptor Loss 0.01).
• PP2: This rule is not applicable for MM-VCEP
• PM1: This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 NOR is it within residues 89-204
• PM5: This is not a missense variant, as this is a non-coding variant, and there has not yet been a different missense change determined to be pathogenic at this amino acid residue.
• PM3: This rule is not applicable for MM-VCEP
• PM4: This variant is not an indel
• PS2: This variant has not been reported in probands in the literature.
• PS4: This variant has not been reported in probands.
• PS3: This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.
• PS1: This is not a missense variant, as this is a non-coding variant, and there has not yet been an amino acid change determined to be pathogenic at this amino acid residue.
• PM6: This variant has not been reported in probands in the literature.