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]
Link to SEPIO compliant JSON-LD document
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001754.5(RUNX1):c.352-141_352-137del

CA320638113

1270876 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2b8e5e1c-120c-4df7-9da4-9892560ca1f3
Approved on: 2024-06-24
Published on: 2024-06-24

HGVS expressions

NM_001754.5:c.352-141_352-137del
NM_001754.5(RUNX1):c.352-141_352-137del
NC_000021.9:g.34880853_34880857del
CM000683.2:g.34880853_34880857del
NC_000021.8:g.36253150_36253154del
CM000683.1:g.36253150_36253154del
NC_000021.7:g.35175020_35175024del
NG_011402.2:g.1108858_1108862del
ENST00000675419.1:c.352-141_352-137del
ENST00000300305.7:c.352-141_352-137del
ENST00000344691.8:c.271-141_271-137del
ENST00000358356.9:c.271-141_271-137del
ENST00000399237.6:c.316-141_316-137del
ENST00000399240.5:c.271-141_271-137del
ENST00000437180.5:c.352-141_352-137del
ENST00000455571.5:c.313-141_313-137del
ENST00000482318.5:c.59-141_59-137del
NM_001001890.2:c.271-141_271-137del
NM_001122607.1:c.271-141_271-137del
NM_001754.4:c.352-141_352-137del
NM_001001890.3:c.271-141_271-137del
NM_001122607.2:c.271-141_271-137del

Likely Benign

Met criteria codes 3
BP4 BP7 PM2_Supporting
Not Met criteria codes 23
PVS1 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP5 PS2 PS4 PS3 PS1 PP1 PP4 PP3 PP2 PM6 PM1 PM5 PM3 PM4

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.352-141_352-137del variant is an intronic variant which is absent from all population databases, including gnomAD v2.1.1 and v3.1.2, with at least 20x coverage for RUNX1 (PM2_supporting). In addition, splicing algorithms predicted no effect on splicing (SpliceAI score < 0.20) (BP4), and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP100way (GRCh38/hg38) scores 0.0926535 to -0.560732 < 2.0 for all deleted nucleotides) (BP7). To our knowledge, this variant has not been found in patients with FPD/AML phenotype, and no functional studies are available. In summary, this variant meets the criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, PM2_supporting.
Met criteria codes
BP4
REVEL score is not applicable to this intronic variant. SpliceAI predicts Acceptor loss 0, Donor loss 0.01, Acceptor gain 0, Donor gain 0.01.
BP7
Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score between 0.0926535 and -0.560732 < 2.0 for all nucleotides within the deleted intronic region. (BP7).
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
This rule is not applicable for MM-VCEP
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No published literature is identified for this variant
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
This rule is not applicable for MM-VCEP
BP1
This rule is not applicable for MM-VCEP
BP5
This rule is not applicable for MM-VCEP
PS2
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
PS3
No published literature is identified for this variant
PS1
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
PP4
This rule is not applicable for MM-VCEP
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
This rule is not applicable for MM-VCEP
PM6
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
This rule is not applicable for MM-VCEP
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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