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.1006T>A (p.Phe336Ile)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014222

532669 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 83663d20-afe7-4dd7-96ac-89b903129343

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.1006T>A

NM_001754.5(RUNX1):c.1006T>A (p.Phe336Ile)

NC_000021.9:g.34792572A>T

CM000683.2:g.34792572A>T

NC_000021.8:g.36164869A>T

CM000683.1:g.36164869A>T

NC_000021.7:g.35086739A>T

NG_011402.2:g.1197140T>A

ENST00000675419.1:c.1006T>A

ENST00000300305.7:c.1006T>A

ENST00000344691.8:c.925T>A

ENST00000399240.5:c.733T>A

ENST00000437180.5:c.1006T>A

ENST00000482318.5:c.*596T>A

NM_001001890.2:c.925T>A

NM_001754.4:c.1006T>A

NM_001001890.3:c.925T>A

Uncertain Significance

PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 PVS1 PM5 PM1 PM3 PM4 PM6 PM2 BA1 BS2 BS4 BS3 BS1 BP7 BP5 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

NM_001754.5(RUNX1):c.1006T>A (p.Phe336Ile) is a missense variant which does not meet any ACMG/AMP criteria. In summary, this variant meets the criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: None

PS4

No proband meeting RUNX1 phenotypic criteria has been observed

PS2

No case study found

PS1

A missense change in amino acid 336 has not been determined to be pathogenic before

PS3

No functional studies found

PP1

No case study found

PP4

This rule is not applicable for MM-VCEP

PP3

This missense variant has a REVEL score <0.88 (0.745)

PP2

This rule is not applicable for MM-VCEP

PVS1

This is not a null variant

PM5

A missense change in amino acid 336 has not been determined to be pathogenic before

PM1

This variant does not affect one of the hotspot residues established by the MM-VCEP for RUNX1

PM3

This rule is not applicable for MM-VCEP

PM4

This is a missense variant

PM6

No case study found

PM2

This variant is present at a MAF of 0.00001037 (0.001037%, 1/96474 ) in the European (non-Finnish) population of gnomAD v2.1

BA1

This variant is present at a MAF of 0.00001037 (0.001037%, 1/96474 ) in the European (non-Finnish) population of gnomAD v2.1

BS2

This rule is not applicable for MM-VCEP

BS4

No case study found

BS3

No functional studies found

BS1

This variant is present at a MAF of 0.00001037 (0.001037%, 1/96474 ) in the European (non-Finnish) population of gnomAD v2.1

BP7

This is a missense variant

BP5

This rule is not applicable for MM-VCEP

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP4

This missense variant has a REVEL score >0.50 (0.745)

BP1

This rule is not applicable for MM-VCEP

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.