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.1196G>C (p.Ser399Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410147803

532653 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f1e46bc0-c2e9-41c8-8045-ef01ea529291

Approved on: 2024-08-01

Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.1196G>C

NM_001754.5(RUNX1):c.1196G>C (p.Ser399Thr)

NC_000021.9:g.34792382C>G

CM000683.2:g.34792382C>G

NC_000021.8:g.36164679C>G

CM000683.1:g.36164679C>G

NC_000021.7:g.35086549C>G

NG_011402.2:g.1197330G>C

ENST00000675419.1:c.1196G>C

ENST00000300305.7:c.1196G>C

ENST00000344691.8:c.1115G>C

ENST00000399240.5:c.923G>C

ENST00000437180.5:c.1196G>C

ENST00000482318.5:c.*786G>C

NM_001001890.2:c.1115G>C

NM_001754.4:c.1196G>C

NM_001001890.3:c.1115G>C

Uncertain Significance

BP4 PM2_Supporting

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

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.1196G>C (p.Ser399Thr)is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant has a REVEL score <0.50 (0.048) and a SpliceAI score <0.20 (0.00) (BP4). 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 and BP4.

BP4

This missense variant has a REVEL score <0.50 (0.048) and SpliceAI score is <0.20 (0.00)

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

PS4

No case studies found

PS2

No case studies found

PS3

No functional studies found

PS1

This amino acid location has not been previously established as a pathogenic variant regardless of nucleotide change

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

This missense variant has a REVEL score <0.50 (0.048) and SpliceAI score is <0.20 (0.00)

PP2

This rule is not applicable for MM-VCEP

PM6

No case studies found

PM5

This amino acid residue has not been seen to be pathogenic or likely pathogenic

PM1

Not within hotspot or defined RHD domain

PM3

This rule is not applicable for MM-VCEP

PM4

Not an in-frame deletion/insertion

PVS1

Not a null variant

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BS1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

BP5

This rule is not applicable for MM-VCEP

BP7

Not a synonymous or intronic variant

BP2

Variant not present in gnomAD

BP1

This rule is not applicable for MM-VCEP

BP3

This rule is not applicable for MM-VCEP

BA1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

Curation History

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