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.285del (p.Asn96fs)

CA2580098637

1897839 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f751a626-31e6-4fb0-b9a0-7428b6bf7c21

HGVS expressions

NM_001754.5:c.285del

NM_001754.5(RUNX1):c.285del (p.Asn96fs)

NC_000021.9:g.34886912del

CM000683.2:g.34886912del

NC_000021.8:g.36259209del

CM000683.1:g.36259209del

NC_000021.7:g.35181079del

NG_011402.2:g.1102803del

ENST00000675419.1:c.285del

ENST00000300305.7:c.285del

ENST00000344691.8:c.204del

ENST00000358356.9:c.204del

ENST00000399237.6:c.249del

ENST00000399240.5:c.204del

ENST00000437180.5:c.285del

ENST00000455571.5:c.246del

ENST00000482318.5:c.59-6196del

NM_001001890.2:c.204del

NM_001122607.1:c.204del

NM_001754.4:c.285del

NM_001001890.3:c.204del

NM_001122607.2:c.204del

Pathogenic

PM5_Supporting PVS1 PM1_Supporting PM2_Supporting

BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM3 PM4 PM6

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_001754.5(RUNX1):c.285del (p.Asn96ThrfsTer26) is a frameshift variant in a gene in which loss-of-function is an established mechanism (Frameshift (+1); c.98-c.779 as per VCEP specifications) (PVS1). This variant affects one of the amino acid residues between 89-204 within the RHD (PM1_supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This frameshift variant is downstream of c.98 in transcript NM_001754.4 (PM5_Supporting). In summary, this variant meets the criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM1_supporting, PM2_supporting, PM5_supporting.

PM5_Supporting

Frameshift variant that is downstream of c.98 (in transcript NM_001754.4).

PVS1

Frameshift (+1); c.98-c.779 as per VCEP specifications

PM1_Supporting

Variant affecting one of the AA residues 89-204 within the RHD.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BS2

Not applicable.

BS4

nil data

BS3

nil data

BS1

PM2 met

BP2

nil data

BP3

Not applicable.

BP4

Not applicable (frameshift).

BP1

Not applicable.

BP5

Not applicable.

BP7

Not applicable (frameshift).

PS2

nil data

PS4

nil data

PS3

nil data

PS1

Not applicable (frameshift).

BA1

PM2 met

PP4

Not applicable.

PP1

nil data

PP3

Not applicable (frameshift).

PP2

Not applicable.

PM3

Not applicable.

PM4

Not applicable (frameshift).

PM6

nil data

Approved on: 2024-03-26

Published on: 2024-03-26

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