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.861C>A (p.Tyr287Ter)

Curation Version - 1.4
Curation History
JSON LD for Version 1.4

CA248619

14467 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fed802a7-8c1d-4396-89f1-65546e996764

Approved on: 2024-03-26

Published on: 2024-03-26

HGVS expressions

NM_001754.5:c.861C>A

NM_001754.5(RUNX1):c.861C>A (p.Tyr287Ter)

NC_000021.9:g.34799407G>T

CM000683.2:g.34799407G>T

NC_000021.8:g.36171704G>T

CM000683.1:g.36171704G>T

NC_000021.7:g.35093574G>T

NG_011402.2:g.1190305C>A

ENST00000675419.1:c.861C>A

ENST00000300305.7:c.861C>A

ENST00000344691.8:c.780C>A

ENST00000399240.5:c.588C>A

ENST00000437180.5:c.861C>A

ENST00000482318.5:c.*451C>A

NM_001001890.2:c.780C>A

NM_001754.4:c.861C>A

NM_001001890.3:c.780C>A

Pathogenic

PP1_Strong PM5_Supporting PS4_Supporting PVS1 PM2_Supporting

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

Evidence Links 1

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:c.861C>A (p.Tyr287Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant was found to co-segregate with disease in multiple affected family members, with seven meioses observed in one family (PP1_Strong; PMID: 11830488). 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 been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 11830488). 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, PP1_Strong, PM2_supporting, PS4_Supporting.

PP1_Strong

At least 7 meioses in the family with FPD/AML.

At least 7 meioses in the family. PubMed:11830488

PM5_Supporting

This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting).

PS4_Supporting

One family with FPD/AML.

One family with FPD/AML. PubMed:11830488

PVS1

Nonsense variant before the c.916 cutoff that predict to undergo NMD

PM2_Supporting

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

PS2

De novo data for this variant has not been reported in literature.

PS1

This variant is not a missense, or synonymous variant.

PS3

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

PP4

This rule is not applicable for MM-VCEP.

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

De novo data for this variant has not been reported in literature.

BA1

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

BS2

This rule is not applicable for MM-VCEP.

BS4

Segregation was not found to be absent in two or more informative meiosis.

At least 7 meioses in the family. PubMed:11830488

BS1

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

BS3

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

BP5

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

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.

Curation History

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