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.322T>A (p.Cys108Ser)

CA410203468

1012038 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2fa612fa-1063-473d-8d71-390bfba02cb7

HGVS expressions

NM_001754.5:c.322T>A

NM_001754.5(RUNX1):c.322T>A (p.Cys108Ser)

NC_000021.9:g.34886872A>T

CM000683.2:g.34886872A>T

NC_000021.8:g.36259169A>T

CM000683.1:g.36259169A>T

NC_000021.7:g.35181039A>T

NG_011402.2:g.1102840T>A

ENST00000675419.1:c.322T>A

ENST00000300305.7:c.322T>A

ENST00000344691.8:c.241T>A

ENST00000358356.9:c.241T>A

ENST00000399237.6:c.286T>A

ENST00000399240.5:c.241T>A

ENST00000437180.5:c.322T>A

ENST00000455571.5:c.283T>A

ENST00000482318.5:c.59-6159T>A

NM_001001890.2:c.241T>A

NM_001122607.1:c.241T>A

NM_001754.4:c.322T>A

NM_001001890.3:c.241T>A

NM_001122607.2:c.241T>A

Uncertain Significance

PP3 PM1_Supporting PM2_Supporting

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

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.322T>A (p.Cys108Ser) is a missense variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). The variant has a REVEL score is ≥0.88 (0.913 )(PP3). This variant affects one of the other residues 108 (AA 89-204) within the RHD (PM1_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, and PM2_supporting

PP3

REVEL score - 0.913 meets cut-off >0.88

PM1_Supporting

This variant affects one of the other residues 108 (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)

PS2

No case studies found

PS4

No case studies found

PS3

No studies found

PS1

N/A

PP4

No case studies found

PP1

No case studies found

PP2

This rule is not applicable for MM-VCEP

PM3

This rule is not applicable for MM-VCEP

PM4

N/A

PM5

N/A

PM6

No case studies found

PVS1

N/A

BA1

Absent in gnomAD

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No studies found

BS1

Absent in gnomAD

BP2

No homozygotes reported in population databases

BP3

This rule is not applicable for MM-VCEP

BP4

Meets PP3

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BP7

N/A

Approved on: 2022-07-08

Published on: 2022-07-08

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