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.463G>C (p.Val155Leu)

CA10014508

1401789 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4405d325-3b23-4e9b-aa17-b65472be23dc

Approved on: 2024-07-11

Published on: 2024-07-11

HGVS expressions

NM_001754.5:c.463G>C

NM_001754.5(RUNX1):c.463G>C (p.Val155Leu)

NC_000021.9:g.34880602C>G

CM000683.2:g.34880602C>G

NC_000021.8:g.36252899C>G

CM000683.1:g.36252899C>G

NC_000021.7:g.35174769C>G

NG_011402.2:g.1109110G>C

ENST00000675419.1:c.463G>C

ENST00000300305.7:c.463G>C

ENST00000344691.8:c.382G>C

ENST00000358356.9:c.382G>C

ENST00000399237.6:c.427G>C

ENST00000399240.5:c.382G>C

ENST00000437180.5:c.463G>C

ENST00000482318.5:c.*53G>C

NM_001001890.2:c.382G>C

NM_001122607.1:c.382G>C

NM_001754.4:c.463G>C

NM_001001890.3:c.382G>C

NM_001122607.2:c.382G>C

Uncertain Significance

PM1_Supporting PP3

BS2 BS4 BS3 BS1 PVS1 PS2 PS4 PS3 PS1 BP2 BP3 BP4 BP1 BP5 BP7 BA1 PP4 PP1 PP2 PM3 PM4 PM5 PM6 PM2

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.463G>C (p.Val155Leu) is a missense variant which is located in the Runt Homology Domain, but does not occur at an established hotspot residue (PM1_supporting). Multiple lines of computational evidence supports a deleterious effect on the gene (REVEL: 0.904, phyloP100way: 7.568) (PP3). In summary, the clinical significance of this variant is uncertain due to insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PP3, PM1_supporting.

PM1_Supporting

Variant affecting an amino acid residue between 89-204 within the RHD.

PP3

REVEL score: 0.904 phlyP100 way: 7.568 SpliceAI: Δ score 0.02

BS2

Not applicable.

BS4

nil data.

BS3

nil data.

BS1

The variant is found in 2 alleles in the South Asian population (MAF 0.00079554% and 0.0065325% among the South Asian genetic ancestry group).

PVS1

Not applicable (missense).

PS2

nil data.

PS4

nil data.

PS3

nil data.

PS1

nil data.

BP2

nil data.

BP3

Not applicable.

BP4

REVEL score: 0.904 phlyP100 way: 7.568 SpliceAI: Δ score 0.02

BP1

Not applicable.

BP5

Not applicable.

BP7

Not applicable (missense).

BA1

The variant is found in 2 alleles in the South Asian population (MAF 0.00079554% and 0.0065325% among the South Asian genetic ancestry group).

PP4

Not applicable.

PP1

nil data.

PP2

Not applicable.

PM3

Not applicable.

PM4

Not applicable (missense).

PM5

nil data.

PM6

nil data.

PM2

The variant is found in 2 alleles in the South Asian population (MAF 0.00079554% and 0.0065325% among the South Asian genetic ancestry group).

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