Variant: NM_001754.4(RUNX1):c.54G>T (p.Met18Ile)

CA10014725

650319 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 63d601ee-e616-4441-84b5-ee21b4241765

Approved on: 2021-01-11

Published on: 2021-01-11

HGVS expressions

NM_001754.4:c.54G>T
NM_001754.4(RUNX1):c.54G>T (p.Met18Ile)
NM_001754.5:c.54G>T
ENST00000300305.7:c.54G>T
ENST00000416754.1:c.54G>T
ENST00000437180.5:c.54G>T
ENST00000455571.5:c.54G>T
ENST00000475045.6:c.54G>T
ENST00000482318.5:c.54G>T
NC_000021.9:g.35048846C>A
CM000683.2:g.35048846C>A
NC_000021.8:g.36421143C>A
CM000683.1:g.36421143C>A
NC_000021.7:g.35343013C>A
NG_011402.2:g.940866G>T

Likely Benign

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

• Met criteria codes: BS1

• Not Met criteria codes: BA1 PP3 PP1 PM5 PM4 PM1 PM2 PM6 PVS1 BS3 BS4 BP4 BP2 BP7 PS1 PS3 PS4

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The NM_001754.4:c.54G>T variant that results in a Met18Ile missense change has an MAF of 0.0002403 (0.02%, 6/24966 alleles) in the African subpopulation of the gnomAD v2.1.1 cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This variant meets criteria to be classified as likely benign based on BS1 alone with no contradictory evidence supporting pathogenicity. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1.

Met criteria codes

• BS1: The variant is reported at a frequency of 0.0002403 (6/24966 African alleles) in gnomAD v2.1.1 and at a frequency of 0.0001190 (5/42016 African alleles) in gnomAD v3. The frequency reported in gnomAD v2 meets criteria for BS1; threshold: >0.00015

Not Met criteria codes

• BA1: Meets BS1
• PP3: The variant has a REVEL score of 0.256; does not meet threshold of >0.75
• PP1: No data currently available
• PM5: No data currently available
• PM4: N/A
• PM1: N/A
• PM2: Meets BS1
• PM6: No data currently available
• PVS1: N/A
• BS3: No data currently available
• BS4: No data currently available
• BP4: The variant has a REVEL score of 0.256; does not meet threshold of <0.15
• BP2: N/A
• BP7: N/A
• PS1: No data currently available
• PS3: No data currently available
• PS4: The variant has not been reported in the germ line of patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge.