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.503del (p.Gly168fs)

CA2573157355

1363605 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7bdeb898-0ff9-4075-aed1-5a45e2a2fb71

HGVS expressions

NM_001754.5:c.503del

NM_001754.5(RUNX1):c.503del (p.Gly168fs)

NC_000021.9:g.34880563del

CM000683.2:g.34880563del

NC_000021.8:g.36252860del

CM000683.1:g.36252860del

NC_000021.7:g.35174730del

NG_011402.2:g.1109150del

ENST00000675419.1:c.503del

ENST00000300305.7:c.503del

ENST00000344691.8:c.422del

ENST00000358356.9:c.422del

ENST00000399237.6:c.467del

ENST00000399240.5:c.422del

ENST00000437180.5:c.503del

ENST00000482318.5:c.*93del

NM_001001890.2:c.422del

NM_001122607.1:c.422del

NM_001754.4:c.503del

NM_001001890.3:c.422del

NM_001122607.2:c.422del

Pathogenic

PM5_Supporting PVS1 PM2_Supporting

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

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

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, PM5_supp, PM2_supp

PM5_Supporting

Frameshift variant that is downstream of c.98

PVS1

This is a null variant predicted to undergo NMD, present in all biologically relevant transcripts (frameshift variant located between c.98-c.758)

PM2_Supporting

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

PS1

This is not a missense variant, and there has not yet been an amino acid change determined to be pathogenic at this amino acid residue.

PS2

This variant has not been found to co-segregate with the disease in the literature.

PS4

This variant has not been reported in probands.

PS3

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PP4

This rule is not applicable for the MM-VCEP

PP1

This variant was not found to co-segregate with disease in multiple affected family members.

PP3

REVEL data only returned for missense/single nucleotide variants

PP2

This rule is not applicable for the MM-VCEP

BA1

Variant is not present in population databases (gnomAD v2.1 or v3.1.2 or v4.0.0)

BS4

This variant has not been reported in affected family members.

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

BS1

Variant is not present in population databases (gnomAD v2.1 or v3.1.2 or v4.0.0)

BS2

This rule is not applicable for the MM-VCEP

PM3

This rule is not applicable for the MM-VCEP

PM1

This is not a missense variant

PM4

This is not an inframe variant

PM6

This variant has not been reported in probands in the literature.

BP5

This rule is not applicable for the MM-VCEP

BP7

This is not a synonymous or intronic variant

BP2

This variant has not been detected in a homozygous state in an individual or in a population database (gnomAD).

BP3

This rule is not applicable for the MM-VCEP

BP4

REVEL data only returned for missense/single nucleotide variants

BP1

This rule is not applicable for the MM-VCEP

Approved on: 2024-03-26

Published on: 2024-03-26

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