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.233T>C (p.Met78Thr)

CA410203840

859484 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: eb2ad958-ac67-41e5-94f9-e077bcd72cd9

Approved on: 2024-09-18

Published on: 2024-09-18

HGVS expressions

NM_001754.5:c.233T>C

NM_001754.5(RUNX1):c.233T>C (p.Met78Thr)

NC_000021.9:g.34886961A>G

CM000683.2:g.34886961A>G

NC_000021.8:g.36259258A>G

CM000683.1:g.36259258A>G

NC_000021.7:g.35181128A>G

NG_011402.2:g.1102751T>C

ENST00000675419.1:c.233T>C

ENST00000300305.7:c.233T>C

ENST00000344691.8:c.152T>C

ENST00000358356.9:c.152T>C

ENST00000399237.6:c.197T>C

ENST00000399240.5:c.152T>C

ENST00000437180.5:c.233T>C

ENST00000455571.5:c.194T>C

ENST00000482318.5:c.59-6248T>C

NM_001001890.2:c.152T>C

NM_001122607.1:c.152T>C

NM_001754.4:c.233T>C

NM_001001890.3:c.152T>C

NM_001122607.2:c.152T>C

Uncertain Significance

PP3 PM2_Supporting

BA1 BP5 BP7 BP2 BP3 BP4 BP1 BS4 BS3 BS1 PP4 PP1 PP2 PS1 PS2 PS4 PS3 PM5 PM3 PM1 PM4 PM6 PVS1

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.233T>C (p.Met78Thr) is a missense variant and is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant has a REVEL score ≥ 0.88 (0.915) (PP3). The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge. 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, PP3

PP3

This missense variant has a REVEL score ≥ 0.88 (0.915) (PP3).

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

BP5

MM-VCEP deemed N/A for RUNX1

BP7

This variant is not a synonymous or intronic variant.

BP2

No data currently available

BP3

This rule is not applicable for MM-VCEP.

BP4

This missense variant does not have a REVEL score < 0.50.

BP1

This rule is not applicable for MM-VCEP.

BS4

No data currently available

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

PP4

MM-VCEP deemed N/A for RUNX1

PP1

No data currently available

PP2

This rule is not applicable for MM-VCEP.

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

PS2

No data currently available

PS4

The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge.

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PM5

There has not yet been a different missense change determined to be pathogenic at this amino acid residue.

PM3

MM-VCEP deemed N/A for RUNX1

PM1

This variant does not affect an amino acid residues 89-204 within the RHD.

PM4

This variant is not an in-frame deletion/insertion.

PM6

No data currently available

PVS1

This variant is not a null variant.

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