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.501del (p.Ser167fs)

CA658824418

561242 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ed51d746-8682-4c1e-b6ef-66feb364fcbe

HGVS expressions

NM_001754.5:c.501del

NM_001754.5(RUNX1):c.501del (p.Ser167fs)

NC_000021.9:g.34880564del

CM000683.2:g.34880564del

NC_000021.8:g.36252861del

CM000683.1:g.36252861del

NC_000021.7:g.35174731del

NG_011402.2:g.1109148del

ENST00000675419.1:c.501del

ENST00000300305.7:c.501del

ENST00000344691.8:c.420del

ENST00000358356.9:c.420del

ENST00000399237.6:c.465del

ENST00000399240.5:c.420del

ENST00000437180.5:c.501del

ENST00000482318.5:c.*91del

NM_001001890.2:c.420del

NM_001122607.1:c.420del

NM_001754.4:c.501del

NM_001001890.3:c.420del

NM_001122607.2:c.420del

Pathogenic

PM2_Supporting PVS1 PM5_Supporting PS4_Supporting

BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS3 PS1 PP1 PP4 PP3 PP2 PM3 PM1 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_001754.4:c.501del (p.Ser167fs) 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). The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge; however one unpublished proband meeting at least one of the RUNX1 phenotype criteria is noted (PS4_Supporting; SCV000807785.1). 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, PS4_Supporting.

PM2_Supporting

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

PVS1

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

PM5_Supporting

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

PS4_Supporting

The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge. From internal laboratory data (SCV000807785.1): 1 patient meeting RUNX1 phenotype criteria

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

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

PS2

No data currently available

PS3

No data currently available

PS1

This variant is not a missense, or synonymous variant.

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

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

Approved on: 2024-03-26

Published on: 2024-03-26

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