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.668A>G (p.Glu223Gly)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014381

532663 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a0ec2209-681c-4062-80e3-bf927658430a

Approved on: 2023-11-13

Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.668A>G

NM_001754.5(RUNX1):c.668A>G (p.Glu223Gly)

NC_000021.9:g.34834547T>C

CM000683.2:g.34834547T>C

NC_000021.8:g.36206844T>C

CM000683.1:g.36206844T>C

NC_000021.7:g.35128714T>C

NG_011402.2:g.1155165A>G

ENST00000675419.1:c.668A>G

ENST00000300305.7:c.668A>G

ENST00000344691.8:c.587A>G

ENST00000358356.9:c.587A>G

ENST00000399237.6:c.632A>G

ENST00000399240.5:c.532+24927A>G

ENST00000437180.5:c.668A>G

ENST00000469087.1:n.204A>G

ENST00000482318.5:c.*258A>G

NM_001001890.2:c.587A>G

NM_001122607.1:c.587A>G

NM_001754.4:c.668A>G

NM_001001890.3:c.587A>G

NM_001122607.2:c.587A>G

Likely Benign

BS1

PM6 PM2 PM1 PM3 PM5 PM4 BA1 BS2 BS4 BS3 BP4 BP3 BP1 BP2 BP5 BP7 PS1 PS2 PS3 PS4 PVS1 PP1 PP2 PP3 PP4

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.668A>G (p.Glu223Gly) is a missense variant. MAF of 0.00084 (0.084%, 13/113452, 13 alleles) in the European (non-Finnish) subpopulation of the gnomAD cohort …) cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1

BS1

MAF of 0.00084 (0.084%, 13/113452, 13 alleles) in the European (non-Finnish) subpopulation of the gnomAD cohort …) cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1)

PM6

No case studies found

PM2

MAF of 0.00084 (0.084%, 13/113452, 13 alleles) in the European (non-Finnish) subpopulation of the gnomAD cohort …) cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1)

PM1

Not at a hotspot or within the critical region

PM3

This rule is not applicable for MM-VCEP

PM5

Novel amino acid has not been previously established as pathogenic

PM4

Not an in-frame deletion/insertion

BA1

MAF of 0.00084 (0.084%, 13/113452, 13 alleles) in the European (non-Finnish) subpopulation of the gnomAD cohort …) cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1)

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BP4

This missense variant has a REVEL score that is not ≥0.88 (0.799) and SpliceAI is ≤0.20 (0.00)

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP2

No homozygotes present in gnomAD

BP5

This rule is not applicable for MM-VCEP

BP7

Not a synonymous or intronic variant

PS1

Amino acid has not been previously established as pathogenic

PS2

No case studies found

PS3

No functional studies found

PS4

This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 31018948) but meets BS1 therefore cannot be applied

PVS1

Not a null variant

PP1

No case studies found

PP2

This rule is not applicable for MM-VCEP

PP3

This missense variant has a REVEL score that is not ≥0.88 (0.799) and SpliceAI is ≤0.20 (0.00)

PP4

This rule is not applicable for MM-VCEP

Curation History

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