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.490G>T (p.Val164Phe)

CA410202501

1437603 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: ccaf1a75-1215-40dc-9640-a79c4e824cf1

Approved on: 2024-10-29

Published on: 2024-10-29

HGVS expressions

NM_001754.5(RUNX1):c.490G>T (p.Val164Phe)

NM_001754.5:c.490G>T

NC_000021.9:g.34880575C>A

CM000683.2:g.34880575C>A

NC_000021.8:g.36252872C>A

CM000683.1:g.36252872C>A

NC_000021.7:g.35174742C>A

NG_011402.2:g.1109137G>T

ENST00000675419.1:c.490G>T

ENST00000300305.7:c.490G>T

ENST00000344691.8:c.409G>T

ENST00000358356.9:c.409G>T

ENST00000399237.6:c.454G>T

ENST00000399240.5:c.409G>T

ENST00000437180.5:c.490G>T

ENST00000482318.5:c.*80G>T

NM_001001890.2:c.409G>T

NM_001122607.1:c.409G>T

NM_001754.4:c.490G>T

NM_001001890.3:c.409G>T

NM_001122607.2:c.409G>T

Uncertain Significance

PM1_Supporting PP3 PM2_Supporting

BA1 BS2 BS4 BS3 BS1 BP7 BP5 BP2 BP3 BP4 BP1 PS4 PS2 PS1 PS3 PP1 PP4 PP2 PVS1 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.490G>T (p.Val164Phe) is a missense variant which affects a residue within the Runt Homology Domain (RHD) established by the MM-VCEP for RUNX1 (Val164) (PM1_supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). It has a REVEL score of 0.959, which is greater than 0.88 (PP3). This variant has been reported in ClinVar; however, no phenotypic data was provided. In summary, this variant meets the criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1_supporting, PP3, PM2_supporting.

PM1_Supporting

This missense variant affects amino acid 164 which is an amino acid residue (89-204) within the RHD.

PP3

REVEL score ≥ 0.88 (REVEL score=0.959)

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

BA1

PM2_supporting met

BS2

This rule is not applicable for MM-VCEP

BS4

No case study found

BS3

No studies found

BS1

PM2_supporting met

BP7

Missense variant with no predicted splice effect

BP5

This rule is not applicable for MM-VCEP

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP4

REVEL score is >0.5

BP1

This rule is not applicable for MM-VCEP

PS4

NO proband meeting RUNX1 FPD-MM phenotypic criteria has been described

PS2

No case study found

PS1

No missense change has been at amino acid 164 has been determined to be pathogenic before

PS3

No studies found

PP1

No case study found

PP4

This rule is not applicable for MM-VCEP

PP2

This rule is not applicable for MM-VCEP

PVS1

This is not a null variant

PM5

No missense change has been at amino acid 164 has been determined to be pathogenic before

PM3

This rule is not applicable for MM-VCEP

PM4

This is a missense variant

PM6

No case study found

Curation History

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