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.447A>C (p.Ala149=)

CA512318720

1142684 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fdc5cdaa-936b-42dd-9c1c-ffb4c241a00a

HGVS expressions

NM_001754.5:c.447A>C

NM_001754.5(RUNX1):c.447A>C (p.Ala149=)

NC_000021.9:g.34880618T>G

CM000683.2:g.34880618T>G

NC_000021.8:g.36252915T>G

CM000683.1:g.36252915T>G

NC_000021.7:g.35174785T>G

NG_011402.2:g.1109094A>C

ENST00000675419.1:c.447A>C

ENST00000300305.7:c.447A>C

ENST00000344691.8:c.366A>C

ENST00000358356.9:c.366A>C

ENST00000399237.6:c.411A>C

ENST00000399240.5:c.366A>C

ENST00000437180.5:c.447A>C

ENST00000455571.5:c.408A>C

ENST00000482318.5:c.*37A>C

NM_001001890.2:c.366A>C

NM_001122607.1:c.366A>C

NM_001754.4:c.447A>C

NM_001001890.3:c.366A>C

NM_001122607.2:c.366A>C

Uncertain Significance

BP4 PM2_Supporting

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

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.447A>C (p.Ala149=) is a synonymous variant. No REVEL score because a synonymous variant and SpliceAI is ≤0.20 (BP4). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets the criteria to be classified as a variant of Uncertain significance - insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and PM2_supporting.

BP4

No REVEL score. SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).

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 evidence found

PS1

N/A

PM3

This rule is not applicable for MM-VCEP

PM1

N/A

PM4

N/A

PM5

N/A

PM6

No case studies found

BA1

Meets PM2_supporting

PVS1

N/A

BP2

No homozygotes observed in gnomAD population (v2 and v3)

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BP7

The c.447A>C (p.Ala149=) variant is a synonymous (silent) variant. SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20). Evolutionary algorithms predict site is conserved - PhyloP score 4.9

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No evidence found

BS1

Meets PM2_supporting

PP4

N/A

PP1

No case studies found

PP3

SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).

PP2

This rule is not applicable for MM-VCEP

Approved on: 2022-07-06

Published on: 2022-07-06

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.