Evidence Repository
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 label mismatch: RUNX1 vs undefined
  • 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.1269C>T (p.Arg423=)

CA10014189

239042 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 35a9e328-f29e-49b8-8ad9-03779bd95996
Approved on: 2025-05-02
Published on: 2025-05-02

HGVS expressions

NM_001754.5:c.1269C>T
NM_001754.5(RUNX1):c.1269C>T (p.Arg423=)
NC_000021.9:g.34792309G>A
CM000683.2:g.34792309G>A
NC_000021.8:g.36164606G>A
CM000683.1:g.36164606G>A
NC_000021.7:g.35086476G>A
NG_011402.2:g.1197403C>T
ENST00000675419.1:c.1269C>T
ENST00000300305.7:c.1269C>T
ENST00000344691.8:c.1188C>T
ENST00000399240.5:c.996C>T
ENST00000437180.5:c.1269C>T
ENST00000482318.5:c.*859C>T
NM_001001890.2:c.1188C>T
NM_001754.4:c.1269C>T
NM_001001890.3:c.1188C>T
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Likely Benign

Met criteria codes 3
BS1 BP7 BP4
Not Met criteria codes 23
PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM3 PM1 PM5 PM4 PM2 PM6 PVS1 BS4 BS3 BS2 BP5 BP2 BP3 BP1

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.1269C>T (p.Arg423=) is a synonymous variant which has a MAF of 0.0003400 (0.034%, 23/67652 alleles) in the European non-Finnish subpopulation of the gnomAD v3 cohort, meeting the threshold for BS1. This variant has a SpliceAI score ≤ 0.20 (0.0) (BP4), and evolutionary conservation algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (0.62)) (BP7). 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, BP4, BP7.
Met criteria codes
BS1
MAF of 0.0003400 (0.034%, 23/67652 alleles) in the European non-Finnish subpopulation of the gnomAD v3 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1).
BP7
This variant has a SpliceAI score ≤ 0.20 (0) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0) (0.62).
BP4
This synonymous variant has a SpliceAI score ≤ 0.20 (0.0).
Not Met criteria codes
PS2
De novo data for this variant has not been reported in literature.
PS4
Proband data for this variant has not been reported in literature.
PS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
PP4
not applicable
PP1
Segregation data for this variant has not been reported in literature.
PP3
This synonymous does not have a REVEL score ≥ 0.88 or a SpliceAI score ≥ 0.38.
PP2
not applicable
PM3
not applicable
PM1
This variant is not a missense variant.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
not applicable
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
De novo data for this variant has not been reported in literature.
PVS1
Not a null variant.
BS4
Segregation data for this variant has not been reported in literature.
BS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
BS2
not applicable
BP5
not applicable
BP2
This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
BP3
not applicable
BP1
not applicable
Curation History
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