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.268del (p.Val90fs)

CA2580098639

1695383 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b0b7aec2-ccb2-4a88-9d47-523b79d149be

HGVS expressions

NM_001754.5:c.268del

NM_001754.5(RUNX1):c.268del (p.Val90fs)

NC_000021.9:g.34886927del

CM000683.2:g.34886927del

NC_000021.8:g.36259224del

CM000683.1:g.36259224del

NC_000021.7:g.35181094del

NG_011402.2:g.1102786del

ENST00000675419.1:c.268del

ENST00000300305.7:c.268del

ENST00000344691.8:c.187del

ENST00000358356.9:c.187del

ENST00000399237.6:c.232del

ENST00000399240.5:c.187del

ENST00000437180.5:c.268del

ENST00000455571.5:c.229del

ENST00000482318.5:c.59-6213del

NM_001001890.2:c.187del

NM_001122607.1:c.187del

NM_001754.4:c.268del

NM_001001890.3:c.187del

NM_001122607.2:c.187del

Pathogenic

PM2_Supporting PVS1 PM5_Supporting

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

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

PM2_Supporting

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

PVS1

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

PM5_Supporting

Frameshift variant that is downstream of c.98

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-VCE

BP7

This is not a synonymous or intronic variant

BP5

This rule is not applicable for the MM-VCE

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-VCE

BP4

REVEL data only returned for missense/single nucleotide variants.

BP1

This rule is not applicable for the MM-VCE

PS2

This variant has not been reported in probands 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.

PS1

Its not a missense variant

PP1

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

PP4

This rule is not applicable for the MM-VCE

PP3

REVEL data only returned for missense/single nucleotide variants.

PP2

This rule is not applicable for the MM-VCE

PM1

This is not a missense variant

PM3

This rule is not applicable for the MM-VCE

PM4

This variant is not an inframe indel

PM6

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

Approved on: 2024-03-26

Published on: 2024-03-26

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