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.351+15A>G

CA10014545

258185 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 94e6e157-486c-4c38-a2be-d9aa1387bd45
Approved on: 2019-07-26
Published on: 2019-08-02

HGVS expressions

NM_001754.4:c.351+15A>G
NM_001754.4(RUNX1):c.351+15A>G
NC_000021.9:g.34886828T>C
CM000683.2:g.34886828T>C
NC_000021.8:g.36259125T>C
CM000683.1:g.36259125T>C
NC_000021.7:g.35180995T>C
NG_011402.2:g.1102884A>G
NM_001001890.2:c.270+15A>G
NM_001122607.1:c.270+15A>G
ENST00000300305.7:c.351+15A>G
ENST00000344691.8:c.270+15A>G
ENST00000358356.9:c.270+15A>G
ENST00000399237.6:c.315+15A>G
ENST00000399240.5:c.270+15A>G
ENST00000437180.5:c.351+15A>G
ENST00000455571.5:c.312+15A>G
ENST00000482318.5:c.59-6115A>G

Benign

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

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.4:c.351+15A>G variant has a MAF of 0.00809 (0.809%, 524/64,760 alleles) in the European (Non-Finnish) subpopulation of the ExAC cohort that is ≥ 0.0015 (0.15%) (BA1). This variant is detected in homozygous state (8) in gnomAD population database (BP2). This intronic 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 (BP4). In addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score -1.34728 < 0.1) (BP7). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2, BP4, BP7.
Met criteria codes
BA1
ExAC Allele Frequency of European (Non-Finnish) Subpopulation: 0.00809 (524 out of 64760 Alleles) > 0.0015
BP7
An intronic 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: -1.34728 <0.1).
BP4
Intronic variant for which SSF and MES predict 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 (8) in gnomAD population database (BP2).
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
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
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
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 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
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
BS3
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 code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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