Evidence Repository - Clinical Genome Resources

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

Variant: NM_001754.5(RUNX1):c.240_241del (p.Glu80fs)

CA658824422

561230 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e51a9323-787c-4449-b2e7-f05afb4a89ed

HGVS expressions

NM_001754.5:c.240_241del

NM_001754.5(RUNX1):c.240_241del (p.Glu80fs)

NC_000021.9:g.34886953_34886954del

CM000683.2:g.34886953_34886954del

NC_000021.8:g.36259250_36259251del

CM000683.1:g.36259250_36259251del

NC_000021.7:g.35181120_35181121del

NG_011402.2:g.1102758_1102759del

ENST00000675419.1:c.240_241del

ENST00000300305.7:c.240_241del

ENST00000344691.8:c.159_160del

ENST00000358356.9:c.159_160del

ENST00000399237.6:c.204_205del

ENST00000399240.5:c.159_160del

ENST00000437180.5:c.240_241del

ENST00000455571.5:c.201_202del

ENST00000482318.5:c.59-6241_59-6240del

NM_001001890.2:c.159_160del

NM_001122607.1:c.159_160del

NM_001754.4:c.240_241del

NM_001001890.3:c.159_160del

NM_001122607.2:c.159_160del

Pathogenic

PM5_Supporting PS4_Moderate PVS1 PM2_Supporting

PS2 PS1 PS3 PP1 PP4 PP3 PP2 BA1 BS4 BS3 BS1 BS2 PM3 PM1 PM4 PM6 BP5 BP7 BP2 BP3 BP4 BP1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

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

The NM_001754.4:c.240_241del (p.Glu80fs) variant is a frameshift variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). Two unpublished probands meeting the RUNX1 phenotype criteria are noted (PS4_Moderate; SCV000807768.1). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting, PS4_Moderate.

PM5_Supporting

This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting).

PS4_Moderate

Proband from PMID: 28933735 has a different nucleotide change. From internal laboratory data (SCV000807768.1): 2 unrelated patients with thrombocytopenia and family history of thrombocytopenia and hematologic malignancy.

PVS1

The variant causes a frameshift that introduces a premature termination codon. The resulting transcript is expected to undergo NMD.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

PS2

No data currently available

PS1

This variant is not a missense, or synonymous variant.

PS3

No data currently available

PP1

No data currently available

PP4

MM-VCEP deemed N/A for RUNX1

PP3

This variant does not have applicable in-silico data available.

PP2

MM-VCEP deemed N/A for RUNX1

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

BS4

No data currently available

BS3

No data currently available

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

BS2

MM-VCEP deemed N/A for RUNX1

PM3

MM-VCEP deemed N/A for RUNX1

PM1

This variant is not a missense variant.

PM4

This variant is not an in-frame deletion/insertion.

PM6

No data currently available

BP5

MM-VCEP deemed N/A for RUNX1

BP7

This variant is not a synonymous or intronic variant.

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

MM-VCEP deemed N/A for RUNX1

BP4

This variant does not have applicable in-silico data available.

BP1

MM-VCEP deemed N/A for RUNX1

Approved on: 2024-03-26

Published on: 2024-03-26

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