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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.1389C>G (p.Pro463=)

CA10014178

258184 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9ae68387-9090-4f9d-933e-8799521dac42
Approved on: 2019-08-02
Published on: 2019-08-02

HGVS expressions

NM_001754.4:c.1389C>G
NM_001754.4(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
NM_001001890.2:c.1308C>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

Benign

Met criteria codes 4
BP7 BP4 BP2 BA1
Not Met criteria codes 14
PS1 PS3 PS4 PP3 PP1 PM5 PM4 PM1 PM6 PM2 PVS1 BS3 BS4 BS1

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The MAF for the synonymous variant, NM_001754.4:c.1389C>G (p.Pro463=) is 0.1206 (12%, 1976/16382 alleles) in the African subpopulation of the gnomAD cohort, which is ≥ 0.0015 (0.15%) (BA1). This variant is predicted by SSF and MES to lead to 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 (BP4). This synonymous variant is predicted by evolutionary conservation prediction algorithms that the site is not conserved (PhyloP score -0.503315 <0.1) (BP7). This variant is detected in a homozygous state in 202 individuals in a gnomAD (BP2). 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
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).
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.
BP2
This variant is detected in homozygous state (202) in gnomAD population database (BP2).
BA1
gnomAD Allele Frequency of 0.1206 (12%, 1976/16382 alleles) in the African subpopulation >0.0015
Not Met criteria codes
PS1
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
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
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No evidence
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
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No evidence
PM2
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
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No data
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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