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.1280G>C (p.Arg427Pro)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410147522

2089328 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bb7a319a-d6b2-43fb-a0b9-3773baca0a6a

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.1280G>C

NM_001754.5(RUNX1):c.1280G>C (p.Arg427Pro)

NC_000021.9:g.34792298C>G

CM000683.2:g.34792298C>G

NC_000021.8:g.36164595C>G

CM000683.1:g.36164595C>G

NC_000021.7:g.35086465C>G

NG_011402.2:g.1197414G>C

ENST00000675419.1:c.1280G>C

ENST00000300305.7:c.1280G>C

ENST00000344691.8:c.1199G>C

ENST00000399240.5:c.1007G>C

ENST00000437180.5:c.1280G>C

ENST00000482318.5:c.*870G>C

NM_001001890.2:c.1199G>C

NM_001754.4:c.1280G>C

NM_001001890.3:c.1199G>C

Uncertain Significance

PM2_Supporting BP4

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

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.1280G>C (p.Arg427Pro) is a missense variant which 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). This missense variant has a REVEL score <0.50 (0.499) (BP4). This variant was reported in ClinVar in 2022 by Invitae, but the affected status of the proband is unknown (Variation ID 2089328). 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, BP4.

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).

BP4

This missense variant has a REVEL score <0.50 (0.499).

PM6

This variant is only reported in one observational study in an unknown number of individuals with RUNX1-phenotypic criteria (PMID: 36436542; PMCID: PMC9886555).

PM1

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

PM5

This variant is a missense change at the same residue (p.Ser417Phe) where one different missense change has been previously established as a variant of uncertain significance (ClinVar ID 409817) based on MM-VCEP rules for RUNX1.

PM3

This rule is not applicable for MM-VCEP.

PM4

This variant is missense.

BA1

This variant is completely absent from all population databases.

PVS1

This variant is missense.

BS4

This variant has no reported segregation data.

BS3

This variant has no reported functional evidence.

BS1

This variant is completely absent from all population databases.

BS2

This rule is not applicable for MM-VCEP.

BP7

This variant is missense.

BP5

This rule is not applicable for MM-VCEP.

BP2

This variant is only reported in one observational study in an unknown number of individuals with phase not confirmed (PMID: 36436542; PMCID: PMC9886555).

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

PS2

This variant is only reported in one observational study in an unknown number of individuals with RUNX1-phenotypic criteria (PMID: 36436542; PMCID: PMC9886555).

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 2089328).

PS3

This variant has no reported functional evidence.

PS1

The variant is not the same amino acid change as a previously established pathogenic variant curated using MM-VCEP rules for RUNX1.

PP1

This variant has no reported segregation data.

PP4

This rule is not applicable for MM-VCEP.

PP3

This missense variant does not have a REVEL score >0.88 (0.499).

PP2

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.