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.189C>G (p.Ala63=)

CA512318936

1135117 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6e04cd15-32d0-435d-a699-22556617ecec

HGVS expressions

NM_001754.5:c.189C>G

NM_001754.5(RUNX1):c.189C>G (p.Ala63=)

NC_000021.9:g.34887005G>C

CM000683.2:g.34887005G>C

NC_000021.8:g.36259302G>C

CM000683.1:g.36259302G>C

NC_000021.7:g.35181172G>C

NG_011402.2:g.1102707C>G

ENST00000675419.1:c.189C>G

ENST00000300305.7:c.189C>G

ENST00000344691.8:c.108C>G

ENST00000358356.9:c.108C>G

ENST00000399237.6:c.153C>G

ENST00000399240.5:c.108C>G

ENST00000437180.5:c.189C>G

ENST00000455571.5:c.150C>G

ENST00000482318.5:c.59-6292C>G

NM_001001890.2:c.108C>G

NM_001122607.1:c.108C>G

NM_001754.4:c.189C>G

NM_001001890.3:c.108C>G

NM_001122607.2:c.108C>G

Uncertain Significance

BP4 PM2_Supporting

PS4 PS2 PS1 PS3 BP5 BP7 BP3 BP1 BP2 PP1 PP4 PP3 PP2 BA1 PM5 PM1 PM4 PM3 PVS1 PM6 BS2 BS4 BS3 BS1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.189C>G (p.Ala63=) is a synonymous variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). Synonymous variant therefore no REVEL score and SplIce is ≤0.20 (0.00)(BP4). 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: BP4 and PM2_supporting

BP4

Synonymous variant therefore no REVEl score and Splice is ≤0.20 (0.00)

PM2_Supporting

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

PS4

No case studies found

PS2

No case studies found

PS1

The amino acid location has not been previously established as pathogenic

PS3

Functional studies not found

BP5

This rule is not applicable for the MMVCEP

BP7

Evolutionary conservation prediction algorithms predict the site as being conserved (phyloP score 3.295541 is not <2.0)

BP3

This rule is not applicable for the MMVCEP

BP1

This rule is not applicable for the MMVCEP

BP2

This variant is completely absent from all population databases therefore no homozygotes present in gnomAD

PP1

No case studies found

PP4

This rule is not applicable for the MMVCEP

PP3

Synonymous variant therefore no REVEl score and SplIce is not ≥0.38(0.00)

PP2

This rule is not applicable for the MMVCEP

BA1

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

PM5

Not a missense variant

PM1

Not a missense variant

PM4

Not an in-frame deletion/insertion

PM3

This rule is not applicable for the MMVCEP

PVS1

Not a null variant

PM6

No case studies found

BS2

This rule is not applicable for the MMVCEP

BS4

No case studies found

BS3

Functional studies not found

BS1

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

Approved on: 2022-07-08

Published on: 2022-07-08

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