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.1389C>G (p.Pro463=)

CA10014178

258184 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9ae68387-9090-4f9d-933e-8799521dac42
Approved on: 2025-05-02
Published on: 2025-05-02

HGVS expressions

NM_001754.5:c.1389C>G
NM_001754.5(RUNX1):c.1389C>G (p.Pro463=)
NC_000021.9:g.34792189G>C
CM000683.2:g.34792189G>C
NC_000021.8:g.36164486G>C
CM000683.1:g.36164486G>C
NC_000021.7:g.35086356G>C
NG_011402.2:g.1197523C>G
ENST00000675419.1:c.1389C>G
ENST00000300305.7:c.1389C>G
ENST00000344691.8:c.1308C>G
ENST00000399240.5:c.1116C>G
ENST00000437180.5:c.1389C>G
ENST00000482318.5:c.*979C>G
NM_001001890.2:c.1308C>G
NM_001754.4:c.1389C>G
NM_001001890.3:c.1308C>G
More

Benign

Met criteria codes 4
BA1 BP7 BP2 BP4
Not Met criteria codes 22
PP4 PP1 PP3 PP2 PVS1 PM2 PM6 PM3 PM1 PM4 PM5 BS2 BS1 BS4 BS3 BP5 BP3 BP1 PS4 PS2 PS3 PS1

Evidence Links 1

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_001754.4(RUNX1):c.1389C>G (p.Pro463=) is a synonymous variant which has a minor allele frequency of 0.1206 (1976/16382 alleles) in the African subpopulation of the gnomAD cohort, meeting the threshold for BA1. It is detected in a homozygous state in 202 individuals in gnomAD (BP2). Splicing predictors SSF and MES indicate no significant impact on the canonical splice site, and no cryptic splice sites are created (BP4). Evolutionary conservation algorithms predict the site as not being conserved (BP7). 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, BP7.
Met criteria codes
BA1
gnomAD Allele Frequency of 0.1206 (12%, 1976/16382 alleles) in the African subpopulation >0.0015
BP7
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved (phyloP100way: -0.503315 <0.1).
BP2
This variant is detected in homozygous state (202) in gnomAD population database (BP2).
BP4
This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created.
Not Met criteria codes
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No evidence
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No evidence
PM3
Not applicable
PM1
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No data
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Reported in multiple individuals but only one patient had MDS. The phenotype reported in other patients did not meet the RUNX1 phenotype criteria
This variant was identified in 2 unrelated patients. The first one was diagnosed with myeloma at the age of 35 and the second one was diagnosed with myelodysplastic syndrome at the age of 50. PubMed:27106701
PS2
No evidence
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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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