Variant: NM_001754.5(RUNX1):c.58+265G>A

CA14902411

1180228 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 550972e3-603e-4ec8-908a-79b6c5c018e5

Approved on: 2022-01-20

Published on: 2022-06-23

HGVS expressions

NM_001754.5:c.58+265G>A
NM_001754.5(RUNX1):c.58+265G>A
NC_000021.9:g.35048577C>T
CM000683.2:g.35048577C>T
NC_000021.8:g.36420874C>T
CM000683.1:g.36420874C>T
NC_000021.7:g.35342744C>T
NG_011402.2:g.941135G>A
ENST00000675419.1:c.58+265G>A
ENST00000300305.7:c.58+265G>A
ENST00000416754.1:c.58+265G>A
ENST00000437180.5:c.58+265G>A
ENST00000455571.5:c.58+265G>A
ENST00000475045.6:c.58+265G>A
ENST00000482318.5:c.58+265G>A
NM_001754.4:c.58+265G>A

Benign

• Met criteria codes: BA1 BP7 BP2 BP4

• Not Met criteria codes: PVS1 BS4 BS3 BS1 BS2 PP1 PP4 PP3 PP2 PM6 PM2 PM1 PM5 PM3 PM4 PS2 PS4 PS3 PS1 BP5 BP3 BP1

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Myeloid Malignancy VCEP

Intronic variant with a MAF of 0.06181 (6.2%, 538/8704 alleles) in the African/African-American subpopulation of the gnomAD v2.1.1 cohort (≥ 0.0015 (0.15%)) (BA1). In addition, this variant is reported in 44 homozygotes in gnomAD v2.1.1 (BP2). Splice AI predicts no impact on splicing ≤ 0.20 (score: 0.00-0.06) (BP4). Intronic variants which SpliceAI ≤ 0.20 AND evolutionary conservation prediction algorithms predict the site as not conserved (phyloP100 way (GRCh38/hg38) ≤2.0). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2, BP4 and BP7.

Met criteria codes

• BA1: MAF of 0.06181 (6.2%, 538/8704 alleles) in the African/African-American subpopulation of the gnomAD v2.1.1 cohort is ≥ 0.0015 (0.15%).
• BP7: Intronic variants which SpliceAI ≤ 0.20 AND evolutionary conservation prediction algorithms predict the site as not conserved (phyloP100 way -1.57148(GRCh38/hg38) ≤2.0).
• BP2: This variant is reported in 44 homozygotes in gnomAD v2.1.1
• BP4: Splice AI predicts no impact on splicing ≤ 0.20 (score: 0.00-0.06)

Not Met criteria codes

• PVS1: N/A
• BS4: N/A
• BS3: No data currently available
• BS1: Meets BA1
• BS2: This rule is not applicable for MM-VCEP
• PP1: N/A
• PP4: This rule is not applicable for MM-VCEP
• PP3: Splice AI predicts no impact on splicing (score: 0.00-0.06)
• PP2: This rule is not applicable for MM-VCEP
• PM6: N/A
• PM2: Meets BA1
• PM1: N/A
• PM5: N/A
• PM3: This rule is not applicable for MM-VCEP
• PM4: N/A
• PS2: N/A
• PS4: Meets BA1
• PS3: No data currently available
• PS1: N/A
• BP5: This rule is not applicable for MM-VCEP
• BP3: This rule is not applicable for MM-VCEP
• BP1: This rule is not applicable for MM-VCEP