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.159del (p.Ser53fs)

CA658824424

561228 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c87368df-0745-4c45-8410-66cf1bc6fd75

HGVS expressions

NM_001754.5:c.159del

NM_001754.5(RUNX1):c.159del (p.Ser53fs)

NC_000021.9:g.34887035del

CM000683.2:g.34887035del

NC_000021.8:g.36259332del

CM000683.1:g.36259332del

NC_000021.7:g.35181202del

NG_011402.2:g.1102677del

ENST00000675419.1:c.159del

ENST00000300305.7:c.159del

ENST00000344691.8:c.78del

ENST00000358356.9:c.78del

ENST00000399237.6:c.123del

ENST00000399240.5:c.78del

ENST00000437180.5:c.159del

ENST00000455571.5:c.120del

ENST00000482318.5:c.59-6322del

NM_001001890.2:c.78del

NM_001122607.1:c.78del

NM_001754.4:c.159del

NM_001001890.3:c.78del

NM_001122607.2:c.78del

Pathogenic

PM2_Supporting PVS1 PM5_Supporting

PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM3 PM1 PM4 PM6 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7

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(RUNX1):c.159del (p.Ser53fs) 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. 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.

PM2_Supporting

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

PVS1

The 1-bp deletion causes a frameshift and results in premature termination of translation. 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).

PS2

No data currently available

PS4

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 (SCV000807764.1): Patients do not meet RUNX1 phenotype criteria.

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS1

This variant is not a missense, or synonymous variant.

BA1

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

PP4

This rule is not applicable for MM-VCEP.

PP1

No data currently available

PP3

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

PP2

This rule is not applicable for MM-VCEP.

PM3

This rule is not applicable for MM-VCEP.

PM1

This variant is not a missense variant.

PM4

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

PM6

No data currently available

BS2

This rule is not applicable for MM-VCEP.

BS4

No data currently available

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS1

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

BP2

No data currently available

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.

BP5

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

Approved on: 2024-03-26

Published on: 2024-03-26

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