The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_001754.5(RUNX1):c.-2C>T

CA10014737

561220 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: ed3e9a69-189b-4d3e-9760-003b73d35603
Approved on: 2025-01-15
Published on: 2025-01-15

HGVS expressions

NM_001754.5:c.-2C>T
NM_001754.5(RUNX1):c.-2C>T
NC_000021.9:g.35048901G>A
CM000683.2:g.35048901G>A
NC_000021.8:g.36421198G>A
CM000683.1:g.36421198G>A
NC_000021.7:g.35343068G>A
NG_011402.2:g.940811C>T
ENST00000675419.1:c.-2C>T
ENST00000300305.7:c.-2C>T
ENST00000416754.1:c.-2C>T
ENST00000437180.5:c.-2C>T
ENST00000455571.5:c.-2C>T
ENST00000475045.6:c.-2C>T
ENST00000482318.5:c.-2C>T
NM_001754.4:c.-2C>T
More

Likely Benign

Met criteria codes 2
BS1 BP2
Not Met criteria codes 23
PP1 PP3 PP2 PP4 PM6 PM2 PM5 PM4 PM3 PVS1 BA1 BS2 BS3 BS4 BP4 BP1 BP3 BP7 BP5 PS4 PS2 PS3 PS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.-2C>T is a 5' UTR substitution variant which has a MAF of 0.0005758 for East Asian chromosomes by gnomAD v4, exceeding the ClinGen Myeloid Malignancy VCEP threshold (>0.00015) (BS1). Additionally, it has been observed in one homozygote in gnomAD v4 (BP2). 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: BS1, BP2.
Met criteria codes
BS1
gnomAD v2: ALL: 0.006719% (17+2/282760) - EAS: 0.09522% (17+2/19954) - FAF (EAS exomes): 0.06320% gnomAD v3: ALL: 0.006719% (16/152046) - EAS: 0.09522% (12/5186) - FAF (EAS exomes): 0.1335% gnomAD v4: ALL: 0.005391% (85+2/1613658) - EAS: 0.07800% (33+2/44872) - FAF (EAS total): 0.05758%
BP2
gnomAD v2: EAS: 17 heterozygotes and 1 homozygote gnomAD v3: No homozygotes gnomAD v4: EAS: 17 heterozygotes and 1 homozygote
Not Met criteria codes
PP1
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PP3
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
PP2
Not applicable
PP4
Not applicable
PM6
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PM2
gnomAD v2: ALL: 0.006719% (17+2/282760) - EAS: 0.09522% (17+2/19954) - FAF (EAS exomes): 0.06320% gnomAD v3: ALL: 0.006719% (16/152046) - EAS: 0.09522% (12/5186) - FAF (EAS exomes): 0.1335% gnomAD v4: ALL: 0.005391% (85+2/1613658) - EAS: 0.07800% (33+2/44872) - FAF (EAS total): 0.05758%
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Not applicable
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
gnomAD v2: ALL: 0.006719% (17+2/282760) - EAS: 0.09522% (17+2/19954) - FAF (EAS exomes): 0.06320% gnomAD v3: ALL: 0.006719% (16/152046) - EAS: 0.09522% (12/5186) - FAF (EAS exomes): 0.1335% gnomAD v4: ALL: 0.005391% (85+2/1613658) - EAS: 0.07800% (33+2/44872) - FAF (EAS total): 0.05758%
BS2
Not applicable
BS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS4
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BP4
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
BP1
Not applicable
BP3
Not applicable
BP7
This 5' UTR variant is located at a nucleotide that is conserved per an evolutionary conservation algorithm (PhyloP score = 2.83942 in GRCh38).
BP5
Not applicable
PS4
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS2
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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