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]

Variant: NM_001754.5(RUNX1):c.967+2_967+5del

CA645614125

945290 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (MONDO:0100083)

Inheritance Mode: Autosomal dominant inheritance

UUID: 8fa5be74-26b6-4d6e-bb6e-ca90b6cdf97a

Approved on: 2023-12-09

Published on: 2023-12-09

HGVS expressions

NM_001754.5:c.967+2_967+5del

NM_001754.5(RUNX1):c.967+2_967+5del

NC_000021.9:g.34799299_34799302del

CM000683.2:g.34799299_34799302del

NC_000021.8:g.36171596_36171599del

CM000683.1:g.36171596_36171599del

NC_000021.7:g.35093466_35093469del

NG_011402.2:g.1190413_1190416del

ENST00000675419.1:c.967+2_967+5del

ENST00000300305.7:c.967+2_967+5del

ENST00000344691.8:c.886+2_886+5del

ENST00000399240.5:c.694+2_694+5del

ENST00000437180.5:c.967+2_967+5del

ENST00000482318.5:c.*557+2_*557+5del

NM_001001890.2:c.886+2_886+5del

NM_001754.4:c.967+2_967+5del

NM_001001890.3:c.886+2_886+5del

Pathogenic

PM2_Supporting PP1_Strong PVS1_Strong PS4_Moderate

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

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.967+2_967+5del is a noncoding variant. This variant was found to co-segregate with disease in multiple affected family members, with seven or more (8) meioses observed in one family/across 1 family (PP1_Strong; PMID: 28240786). Skips exon 8 with in frame del270- 323 and D269A deletion in TAD(PVS1_strong). This variant has been reported in two or three probands (X) meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 28240786, doi: 10.1093/ajcp/aqz121.026) (PS4_moderate). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). 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: PP1_strong, PVS1_strong, PS4_moderate, PM2_supporting

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

PP1_Strong

This variant was found to co-segregate with disease in multiple affected family members, with seven or more (8) meioses observed in one family/across 1 family (PP1_Strong; PMID: 28240786.

PVS1_Strong

Skip exon 8 with in frame del270- 323 and D269A deletion in TAD

PS4_Moderate

PS4_Moderate: This variant has been reported in two or three probands (X) meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 28240786, doi: 10.1093/ajcp/aqz121.026 ).

BP5

not applicable

BP7

Not applicable

BP2

not applicable

BP3

Not applicable

BP4

Not applicable

BP1

not applicable

BS2

not applicable

BS4

not seen in unaffected individuals in reported families

BS3

no data

BS1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

PP4

not applicable

PP3

Not applicable

PP2

not applicable

PM3

not applicable

PM4

Not applicable

PM5

Not applicable

PM6

nil data

PS2

nil data

PS3

no data

PS1

Not applicable

BA1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.