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.256C>G (p.Pro86Ala)

CA320642689

1003438 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 0315aad9-cc28-49c3-8eab-0c56997a3c62

Approved on: 2024-08-12

Published on: 2024-08-12

HGVS expressions

NM_001754.5:c.256C>G

NM_001754.5(RUNX1):c.256C>G (p.Pro86Ala)

NC_000021.9:g.34886938G>C

CM000683.2:g.34886938G>C

NC_000021.8:g.36259235G>C

CM000683.1:g.36259235G>C

NC_000021.7:g.35181105G>C

NG_011402.2:g.1102774C>G

ENST00000675419.1:c.256C>G

ENST00000300305.7:c.256C>G

ENST00000344691.8:c.175C>G

ENST00000358356.9:c.175C>G

ENST00000399237.6:c.220C>G

ENST00000399240.5:c.175C>G

ENST00000437180.5:c.256C>G

ENST00000455571.5:c.217C>G

ENST00000482318.5:c.59-6225C>G

NM_001001890.2:c.175C>G

NM_001122607.1:c.175C>G

NM_001754.4:c.256C>G

NM_001001890.3:c.175C>G

NM_001122607.2:c.175C>G

Uncertain Significance

PM2_Supporting

PM6 PM5 PM1 PM4 PM3 BA1 BS2 BS4 BS1 BS3 PS4 PS2 PS1 PS3 PVS1 BP7 BP5 BP3 BP2 BP4 BP1 PP1 PP4 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.256C>G (p.Pro86Ala) is a missense variant which is located outside of the Runt Homology Domain. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). The variant has a REVEL score of 0.561, which does not meet the threshold for PP3 (≥0.88) or BP4 (<0.50). 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

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

PM6

No case study found

PM5

A pathogenic missense change has not been reported at amino acid 86

PM1

Amino acid 86, is not a hotspot residue within the RHD according to MM-VCEP rules.

PM4

Missense variant

PM3

This rule is not applicable for MM-VCEP

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS2

This rule is not applicable for MM-VCEP

BS4

No case study found

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

This rule is not applicable for MM-VCEP

PS4

No case study was found. Seen once in ClinVar.

PS2

No case study found

PS1

This amino acid change has not been reported as pathogenic previously

PS3

No functional assays found

PVS1

Missense variant

BP7

Missense variant

BP5

This rule is not applicable for MM-VCEP

BP3

Missense variant

BP2

No case study found

BP4

REVEL sore= 0.561, which is >0.5. SpliceAI predicts on splicing effect

BP1

This rule is not applicable for MM-VCEP

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

REVEL sore= 0.561, which is <0.88. SpliceAI predicts on splicing effect

PP2

This rule is not applicable for MM-VCEP

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