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.424del (p.Ala142fs)

CA645607374

2759299 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a51923b3-48de-4c9b-b191-5561de3402a2

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.424del

NM_001754.5(RUNX1):c.424del (p.Ala142fs)

NC_000021.9:g.34880642del

CM000683.2:g.34880642del

NC_000021.8:g.36252939del

CM000683.1:g.36252939del

NC_000021.7:g.35174809del

NG_011402.2:g.1109071del

ENST00000675419.1:c.424del

ENST00000300305.7:c.424del

ENST00000344691.8:c.343del

ENST00000358356.9:c.343del

ENST00000399237.6:c.388del

ENST00000399240.5:c.343del

ENST00000437180.5:c.424del

ENST00000455571.5:c.385del

ENST00000482318.5:c.*14del

NM_001001890.2:c.343del

NM_001122607.1:c.343del

NM_001754.4:c.424del

NM_001001890.3:c.343del

NM_001122607.2:c.343del

Pathogenic

PM5_Supporting PM2_Supporting PVS1

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

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

NM_001754.5(RUNX1):c.424del (p.Ala142LeufsTer3) is a frameshift variant which is predicted to undergo nonsense-mediated decay in a gene where loss-of-function is an established mechanism (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is downstream of c.98 (PM5_supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting.

PM5_Supporting

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

PM2_Supporting

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

PVS1

This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (-) c.98-c.758 as per VCEP specifications) (PVS1).

PS2

nil data

PS3

NMD predicted

PS1

This variant is not a missense variant.

BA1

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

PP1

nil data

PP4

This rule is not applicable for MM-VCEP.

PP3

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

PP2

This rule is not applicable for MM-VCEP.

PM1

This variant is not a missense variant.

PM3

This rule is not applicable for MM-VCEP.

PM4

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

PM6

nil data

BS2

This rule is not applicable for MM-VCEP.

BS4

nil data

BS3

NMD predicted

BS1

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

BP2

nil data

BP3

This rule is not applicable for MM-VCEP.

BP4

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

BP1

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for MM-VCEP.

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