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.99T>C (p.Asp33=)

CA512319003

436612 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 1eb50d20-5255-4396-9165-7e7d0c1afaca

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.99T>C

NM_001754.5(RUNX1):c.99T>C (p.Asp33=)

NC_000021.9:g.34887095A>G

CM000683.2:g.34887095A>G

NC_000021.8:g.36259392A>G

CM000683.1:g.36259392A>G

NC_000021.7:g.35181262A>G

NG_011402.2:g.1102617T>C

ENST00000675419.1:c.99T>C

ENST00000300305.7:c.99T>C

ENST00000344691.8:c.18T>C

ENST00000358356.9:c.18T>C

ENST00000399237.6:c.63T>C

ENST00000399240.5:c.18T>C

ENST00000437180.5:c.99T>C

ENST00000455571.5:c.60T>C

ENST00000475045.6:c.99T>C

ENST00000482318.5:c.59-6382T>C

NM_001001890.2:c.18T>C

NM_001122607.1:c.18T>C

NM_001754.4:c.99T>C

NM_001001890.3:c.18T>C

NM_001122607.2:c.18T>C

Uncertain Significance

PM2_Supporting

BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM3 PM1 PM4 PM5 PM6 PVS1 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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.99T>C (p.Asp33=) is a synonymous variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant has a SpliceAI predicted acceptor loss of 0.32, which indicates it may impact splicing (BP4/BP7 not applied). 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.

PM2_Supporting

absent from gnomAD V2 and V3 This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BS2

nil data

BS4

nil data

BS3

no data

BS1

absent from gnomAD V2 and V3

BP5

not applicable

BP7

PhyloP score: 3.194, SpliceAI Acceptor Loss 0.32 Δ score

BP2

not applicable

BP3

not applicable

BP4

SpliceAI: Δ type Δ score pre-mRNA position Acceptor Loss 0.32 1 bp Donor Loss 0.09 196 bp Acceptor Gain 0.02 1305 bp Donor Gain 0.00

BP1

not applicable

PS2

nil data

PS4

nil data

PS3

no data

PS1

not applicable

PP4

not applicable

PP1

nil data

PP3

SpliceAI: Δ type Δ score pre-mRNA position Acceptor Loss 0.32 1 bp Donor Loss 0.09 196 bp Acceptor Gain 0.02 1305 bp Donor Gain 0.00

PP2

not applicable

PM3

not applicable

PM1

no data

PM4

not applicable

PM5

not applicable

PM6

nil data

PVS1

not applicable

BA1

absent from gnomAD V2 and V3

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