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.397A>G (p.Met133Val)

CA410202702

2815164 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f9177de0-67c1-4362-bed7-a77022175bec

Approved on: 2024-09-12

Published on: 2024-09-12

HGVS expressions

NM_001754.5:c.397A>G

NM_001754.5(RUNX1):c.397A>G (p.Met133Val)

NC_000021.9:g.34880668T>C

CM000683.2:g.34880668T>C

NC_000021.8:g.36252965T>C

CM000683.1:g.36252965T>C

NC_000021.7:g.35174835T>C

NG_011402.2:g.1109044A>G

ENST00000675419.1:c.397A>G

ENST00000300305.7:c.397A>G

ENST00000344691.8:c.316A>G

ENST00000358356.9:c.316A>G

ENST00000399237.6:c.361A>G

ENST00000399240.5:c.316A>G

ENST00000437180.5:c.397A>G

ENST00000455571.5:c.358A>G

ENST00000482318.5:c.104A>G

NM_001001890.2:c.316A>G

NM_001122607.1:c.316A>G

NM_001754.4:c.397A>G

NM_001001890.3:c.316A>G

NM_001122607.2:c.316A>G

Uncertain Significance

PM1_Supporting PM2_Supporting

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

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.397A>G (p.Met133Val) is a missense variant which is located within the Runt Homology Domain (AA 89-204), but does not occur in an established hotspot residue (PM1_supporting). 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, PM1_supporting.

PM1_Supporting

This variant affects an amino acid residue 89-204 within the RHD.

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.

PS4

Proband data for this variant has not been reported in literature.

PS3

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

PS1

Other changes at this AA residue have not been reported as pathogenic.

BA1

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

PP4

This rule is not applicable for MM-VCEP.

PP1

Segregation data for this variant has not been reported in literature.

PP3

This missense variant does not have a REVEL score ≥ 0.88.

PP2

This rule is not applicable for MM-VCEP.

PM3

This rule is not applicable for MM-VCEP.

PM4

This variant is not an indel.

PM5

Other changes at this AA residue have not been reported as pathogenic.

PM6

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

BS2

This rule is not applicable for MM-VCEP.

BS4

Segregation data for this variant has not been reported in literature.

BS3

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

BS1

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

BP2

This variant has not been reported 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 variant is not an indel.

BP4

This missense variant does not have a REVEL score < 0.50.

BP1

This rule is not applicable for MM-VCEP.

BP5

This rule is not applicable for MM-VCEP.

BP7

This is not a synonymous variant.

PVS1

This is not a null variant.

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