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.505dup (p.Arg169fs)

CA645607320

1996224 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f26a7402-7294-48cd-a15e-f63bdd463654

HGVS expressions

NM_001754.5:c.505dup

NM_001754.5(RUNX1):c.505dup (p.Arg169fs)

NC_000021.9:g.34880561dup

CM000683.2:g.34880561dup

NC_000021.8:g.36252858dup

CM000683.1:g.36252858dup

NC_000021.7:g.35174728dup

NG_011402.2:g.1109152dup

ENST00000675419.1:c.505dup

ENST00000300305.7:c.505dup

ENST00000344691.8:c.424dup

ENST00000358356.9:c.424dup

ENST00000399237.6:c.469dup

ENST00000399240.5:c.424dup

ENST00000437180.5:c.505dup

ENST00000482318.5:c.*95dup

NM_001001890.2:c.424dup

NM_001122607.1:c.424dup

NM_001754.4:c.505dup

NM_001001890.3:c.424dup

NM_001122607.2:c.424dup

Pathogenic

PM5_Supporting PVS1 PM2_Supporting PM1

BS2 BS4 BS3 BS1 BP2 BP3 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.505dup (p.Arg169LysfsTer?) 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). The variant affects the R169 amino acid residue within the RHD (PM1). 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, 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

PM2_Supporting

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

PM1

Variant affecting the R169 AA residue within the RHD.

BS2

Not applicable.

BS4

nil data

BS3

The variant was reported in the literature/databases only as somatic and no functional studies are present (COSMIC: Genomic Mutation ID: COSV55869157; PMID: 30205045).

BS1

PM2 met.

BP2

nil data

BP3

Not applicable.

BP1

Not applicable.

BP5

Not applicable.

BP7

Not applicable (frameshift).

PS2

nil data

PS4

nil data (as germline).

PS3

The variant was reported in the literature/databases only as somatic and no functional studies are present (COSMIC: Genomic Mutation ID: COSV55869157; PMID: 30205045).

PS1

Not applicable (frameshift).

BA1

PM2 met.

PP4

Not applicable.

PP1

nil data

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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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