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.599C>A (p.Pro200His)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410207960

1004688 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 149407af-db7c-48f3-a958-05ee667b179e

Approved on: 2024-08-12

Published on: 2024-08-12

HGVS expressions

NM_001754.5:c.599C>A

NM_001754.5(RUNX1):c.599C>A (p.Pro200His)

NC_000021.9:g.34859488G>T

CM000683.2:g.34859488G>T

NC_000021.8:g.36231785G>T

CM000683.1:g.36231785G>T

NC_000021.7:g.35153655G>T

NG_011402.2:g.1130224C>A

ENST00000675419.1:c.599C>A

ENST00000300305.7:c.599C>A

ENST00000344691.8:c.518C>A

ENST00000358356.9:c.518C>A

ENST00000399237.6:c.563C>A

ENST00000399240.5:c.518C>A

ENST00000437180.5:c.599C>A

ENST00000467577.1:n.91C>A

ENST00000482318.5:c.*189C>A

NM_001001890.2:c.518C>A

NM_001122607.1:c.518C>A

NM_001754.4:c.599C>A

NM_001001890.3:c.518C>A

NM_001122607.2:c.518C>A

Uncertain Significance

PM1_Supporting PP3 PM2_Supporting

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

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.599C>A (p.Pro200His) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). It has a REVEL score of 0.947 (REVEL score ≥ 0.88), meeting PP3. This missense variant is located within the Runt Homology Domain (AA 89-204), but does not occur in an established hotspot residue (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: PM1_supporting, PM2_supporting, and PP3.

PM1_Supporting

Meets PM1_supporting. Variant affecting one of the other amino acid residues 89-204 within the RHD.

PP3

REVEL score= 0.947 (REVELscore ≥ 0.88)

PM2_Supporting

Variant is absent from control population databases. PM2_supporting

PS4

No case study found

PS2

No case study found

PS1

This amino acid change at residue 200 has not been determined to be pathogenic before

PS3

No study found

BA1

Variant is absent from control population databases. PM2_supporting met

PP1

No case study found

PP4

This rule is not applicable for MM-VCEP

PP2

This rule is not applicable for MM-VCEP

PM6

No case study found

PM5

A Missense change at amino acid residue 200 has not been determined to be pathogenic before

PM4

This is a missense variant

PM3

This rule is not applicable for MM-VCEP

PVS1

This is a missense variant

BS4

No case study found

BS3

No study found

BS1

Variant is absent from control population databases. PM2_supporting met

BS2

This rule is not applicable for MM-VCEP

BP7

This is a missense variant

BP5

This rule is not applicable for MM-VCEP

BP3

This is a missense variant

BP2

No case study found

BP4

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

Curation History

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