Variant: NM_001754.4(RUNX1):c.630A>G (p.Leu210=)

CA10014389

464000 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 531a859a-dd57-4409-94fa-a7eb525c21d1

HGVS expressions

NM_001754.4:c.630A>G
NM_001754.4(RUNX1):c.630A>G (p.Leu210=)
NC_000021.9:g.34834585T>C
CM000683.2:g.34834585T>C
NC_000021.8:g.36206882T>C
CM000683.1:g.36206882T>C
NC_000021.7:g.35128752T>C
NG_011402.2:g.1155127A>G
ENST00000675419.1:c.630A>G
ENST00000300305.7:c.630A>G
ENST00000344691.8:c.549A>G
ENST00000358356.9:c.549A>G
ENST00000399237.6:c.594A>G
ENST00000399240.5:c.532+24889A>G
ENST00000437180.5:c.630A>G
ENST00000469087.1:n.166A>G
ENST00000482318.5:c.*220A>G
NM_001001890.2:c.549A>G
NM_001122607.1:c.549A>G
NM_001001890.3:c.549A>G
NM_001122607.2:c.549A>G
NM_001754.5:c.630A>G
NM_001754.5(RUNX1):c.630A>G (p.Leu210=)

Uncertain Significance

• Met criteria codes: BP4

• Not Met criteria codes: BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 PVS1 PS3 PS2 PS4 PS1 BA1 PP1 PP4 PP3 PP2 PM6 PM2 PM1 PM5 PM3 PM4

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

This c.630A>G (p.Leu210=) synonymous variant is not predicted to have any splicing impact per SpliceAI (BP4), but it is located at a moderately conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP score = 2.5748 in GRCh38). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4.

Met criteria codes

• BP4: SpliceAI does not show any significant splicing impact (Δ scores ≤ 0.20).

Not Met criteria codes

• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: MAF<0.015% gnomAD v2: ALL: 0.002487% (7/281408) - NFE: 0.003121% (4/128160) - AMR: 0.008472% (3/35412) gnomAD v3: ALL: 0.001985% (3/151144) - NFE: 0.004417% (3/67926)
• BS2: Not applicable
• BP5: Not applicable
• BP7: Synonymous variant located at a moderately conserved nucleotide (PhyloP = 2.5748 in GRCh38), and the variant is not the reference nucleotide in one primate and/or 3 mammals. SpliceAI does not show a splicing impact.
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP3: Not applicable
• BP1: Not applicable
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: No literature found in HGMD, Google+Google Scholar searches, or COSMIC by NM_001754 or NM_001001890.
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: MAF<0.15% gnomAD v2: ALL: 0.002487% (7/281408) - NFE: 0.003121% (4/128160) - AMR: 0.008472% (3/35412) gnomAD v3: ALL: 0.001985% (3/151144) - NFE: 0.004417% (3/67926)
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: Not applicable
• PP3: SpliceAI does not show any significant splicing impact (Δ scores ≤ 0.20).
• PP2: Not applicable
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: gnomAD v2: ALL: 0.002487% (7/281408) - NFE: 0.003121% (4/128160) - AMR: 0.008472% (3/35412) gnomAD v3: ALL: 0.001985% (3/151144) - NFE: 0.004417% (3/67926)
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: Not applicable
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2022-07-07

Published on: 2022-07-07