Variant: NM_001754.5(RUNX1):c.509-19C>T

CA320618045

1670366 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 060cdf44-9de8-4a43-abfa-6106ea26735c

Approved on: 2024-08-28

Published on: 2024-08-28

HGVS expressions

NM_001754.5:c.509-19C>T
NM_001754.5(RUNX1):c.509-19C>T
NC_000021.9:g.34859597G>A
CM000683.2:g.34859597G>A
NC_000021.8:g.36231894G>A
CM000683.1:g.36231894G>A
NC_000021.7:g.35153764G>A
NG_011402.2:g.1130115C>T
ENST00000675419.1:c.509-19C>T
ENST00000300305.7:c.509-19C>T
ENST00000344691.8:c.428-19C>T
ENST00000358356.9:c.428-19C>T
ENST00000399237.6:c.473-19C>T
ENST00000399240.5:c.428-19C>T
ENST00000437180.5:c.509-19C>T
ENST00000482318.5:c.*99-19C>T
NM_001001890.2:c.428-19C>T
NM_001122607.1:c.428-19C>T
NM_001754.4:c.509-19C>T
NM_001001890.3:c.428-19C>T
NM_001122607.2:c.428-19C>T

Likely Benign

• Met criteria codes: BP4 BP7

• Not Met criteria codes: BS2 BS4 BS3 BS1 PS2 PS3 PS1 PVS1 BP2 BP3 BP1 BP5 BA1 PP4 PP1 PP3 PP2 PM3 PM4 PM1 PM5 PM6 PM2

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.509-19C>T is an intronic variant in intron 5. It is reported at very low levels in gnomAD (0.00003), thus it is not absent but does not meet thresholds for BA1 or BS1. The nucleotide and surrounding sequence are not evolutionarily conserved, and the variant is not predicted to affect splicing, with a SpliceAI score ≤ 0.20 and a phyloP100 way score ≤ 2.0 (1.319) (BP4, BP7). The variant has not been described in the literature. 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.

Met criteria codes

• BP4: Splice AI ≤ 0.20 (0.00)
• BP7: SpliceAI ≤ 0.20 AND phyloP100 way ≤2.0 (1.319).

Not Met criteria codes

• BS2: This rule is not applicable for the MM-VCEP.
• BS4: Clinical data is not available for this variant.
• BS3: Functional data is not available for this variant.
• BS1: This variant has an allele frequency of 0.00003 in the Admixed American population, which is not between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.
• PS2: Clinical data is not available for this variant.
• PS3: Functional data is not available for this variant.
• PS1: This variant is intronic and other variants at this locus have not previously been reported as pathogenic.
• PVS1: This variant is not a null variant.
• BP2: Segregation data is not available for this variant.
• BP3: This is not an in-frame insertion/deletion
• BP1: This rule is not applicable for the MM-VCEP
• BP5: This rule is not applicable for the MM-VCEP.
• BA1: This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset
• PP4: This rule is not applicable for the MM-VCEP.
• PP1: Clinical data is not available for this variant.
• PP3: REVEL data is not available for this variant and Splice AI is 0.00.
• PP2: This rule is not applicable for the MM-VCEP
• PM3: This rule is not applicable for the MM-VCEP.
• PM4: This is not an in-frame insertion/deletion
• PM1: This variant is not located within a hotspot or functional domain.
• PM5: This variant is intronic and other variants at this locus have not previously been reported as pathogenic.
• PM6: Clinical data is not available for this variant.
• PM2: This variant has an allele frequency of 0.00003 in the Admixed American population and is not absent.