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.883_885del (p.Ser295del)

CA10014274

464012 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d3ccbabc-1cf6-4e49-a14d-8153f36437f5

Approved on: 2024-09-25

Published on: 2024-09-25

HGVS expressions

NM_001754.5:c.883_885del

NM_001754.5(RUNX1):c.883_885del (p.Ser295del)

NC_000021.9:g.34799385_34799387del

CM000683.2:g.34799385_34799387del

NC_000021.8:g.36171682_36171684del

CM000683.1:g.36171682_36171684del

NC_000021.7:g.35093552_35093554del

NG_011402.2:g.1190327_1190329del

ENST00000675419.1:c.883_885del

ENST00000300305.7:c.883_885del

ENST00000344691.8:c.802_804del

ENST00000399240.5:c.610_612del

ENST00000437180.5:c.883_885del

ENST00000482318.5:c.*473_*475del

NM_001001890.2:c.802_804del

NM_001754.4:c.883_885del

NM_001001890.3:c.802_804del

Uncertain Significance

PM2_Supporting

BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP3 BP4 BP1 PVS1 PS2 PS4 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM6 PM1 PM5 PM3 PM4

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

NM_001754.5(RUNX1):c.883_885del (p.Ser295del) is an in-frame deletion. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting).

BS4

This variant has no data demonstrating segregation in affected family members.

BS3

This variant has no functional studies demonstrating damaging effect on protein function or splicing.

BS1

This variant is completely absent from all population databases.

BS2

This rule is not applicable for MM-VCEP.

BP7

This variant is an in-frame deletion.

BP5

This rule is not applicable for MM-VCEP.

BP2

This in-frame deletion does not have any observed cases reported in the literature.

BP3

This rule is not applicable for MM-VCEP.

BP4

This variant is an in-frame deletion.

BP1

This rule is not applicable for MM-VCEP.

PVS1

This variant is an in-frame deletion.

PS2

This in-frame deletion does not have data on cases in patients with the disease and no family history.

PS4

This rule is not applicable because there is no published information on affected individuals nor a RUNX1 case control study. This variant was reported in ClinVar in 2022 by Invitae but the affected status of the proband is unknown (Variation ID 464012).

PS3

This variant has no functional studies demonstrating damaging effect on the gene or gene product.

PS1

This variant is an in-frame deletion.

BA1

This variant is completely absent from all population databases.

PP1

This variant has no data demonstrating cosegregation with disease in multiple affected family members in RUNX1.

PP4

This rule is not applicable for MM-VCEP.

PP3

This variant is an in-frame deletion.

PP2

This rule is not applicable for MM-VCEP.

PM6

This in-frame deletion does not have data on probands meeting at least one of the RUNX1-phenotypic criteria with assumed de novo occurrences.

PM1

This in-frame deletion does not affect one of the hotspot residues established by the MM-VCEP for RUNX1.

PM5

This variant is an in-frame deletion.

PM3

This rule is not applicable for MM-VCEP.

PM4

This in-frame deletion/insertion does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.

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