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.403G>A (p.Gly135Ser)

CA410202687

988857 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3caac7dd-021b-484d-a55e-c38c7cbca822

HGVS expressions

NM_001754.5:c.403G>A

NM_001754.5(RUNX1):c.403G>A (p.Gly135Ser)

NC_000021.9:g.34880662C>T

CM000683.2:g.34880662C>T

NC_000021.8:g.36252959C>T

CM000683.1:g.36252959C>T

NC_000021.7:g.35174829C>T

NG_011402.2:g.1109050G>A

ENST00000675419.1:c.403G>A

ENST00000300305.7:c.403G>A

ENST00000344691.8:c.322G>A

ENST00000358356.9:c.322G>A

ENST00000399237.6:c.367G>A

ENST00000399240.5:c.322G>A

ENST00000437180.5:c.403G>A

ENST00000455571.5:c.364G>A

ENST00000482318.5:c.110G>A

NM_001001890.2:c.322G>A

NM_001122607.1:c.322G>A

NM_001754.4:c.403G>A

NM_001001890.3:c.322G>A

NM_001122607.2:c.322G>A

Uncertain Significance

PM1_Supporting PM2_Supporting PP3 PS4_Supporting

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

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.403G>A (p.Gly135Ser) is a missense variant. This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 32935436). This missense variant has a REVEL score >0.88 (0.961) (PP3). This variant affects one of the other residues (AA 89-204) within the RHD (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: PP3, PM1_supporting, PM2_supporting and PS4_supporting.

PM1_Supporting

This variant affects one of the other residues (AA 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).

PP3

This missense variant has a REVEL score >0.88 (0.961)

PS4_Supporting

This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 32935436)

BA1

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

PVS1

Not applicable

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).

BS2

This rule is not applicable for MM-VCEP

BP7

Not a synonymous/ intronic variant

BP5

This rule is not applicable for MM-VCEP

BP4

This missense variant has a REVEL score >0.88 (0.961)

BP1

This rule is not applicable for MM-VCEP

BP2

variant absent in gnomAD

BP3

This rule is not applicable for MM-VCEP

PS2

No case studies found

PS3

No functional studies found

PS1

MMVCEP has not curated a variant previously considered as LP/P

PP1

No case studies found

PP2

This rule is not applicable for MM-VCEP

PP4

This rule is not applicable for MM-VCEP

PM5

Not found

PM3

This rule is not applicable for MM-VCEP

PM4

Not an inframe deletion/ insertion

PM6

No case studies found

Approved on: 2022-06-30

Published on: 2022-06-30

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