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.301G>C (p.Val101Leu)

CA410203589

2864169 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: afbc5661-b1a2-4bbc-91fa-8c38702e6d99

Approved on: 2024-09-30

Published on: 2024-09-30

HGVS expressions

NM_001754.5:c.301G>C

NM_001754.5(RUNX1):c.301G>C (p.Val101Leu)

NC_000021.9:g.34886893C>G

CM000683.2:g.34886893C>G

NC_000021.8:g.36259190C>G

CM000683.1:g.36259190C>G

NC_000021.7:g.35181060C>G

NG_011402.2:g.1102819G>C

ENST00000675419.1:c.301G>C

ENST00000300305.7:c.301G>C

ENST00000344691.8:c.220G>C

ENST00000358356.9:c.220G>C

ENST00000399237.6:c.265G>C

ENST00000399240.5:c.220G>C

ENST00000437180.5:c.301G>C

ENST00000455571.5:c.262G>C

ENST00000482318.5:c.59-6180G>C

NM_001001890.2:c.220G>C

NM_001122607.1:c.220G>C

NM_001754.4:c.301G>C

NM_001001890.3:c.220G>C

NM_001122607.2:c.220G>C

Uncertain Significance

PP3 PM1_Supporting PM2_Supporting

BS4 BS3 BS1 BP7 BP3 BP4 BP1 PS2 PS3 PS1 PP1 PP2 PP4 PM4 PM5 PM6 BA1

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.301G>C (p.Val101Leu) is a missense variant within the Runt Homology domain (AA 89-204), but does not affect an established hotspot variant (PM1_supporting). This missense variant has a REVEL score ≥ 0.88 (0.921) (PP3). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). 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: PM1_supporting, PP3, PM2_supporting.

PP3

This missense variant has a REVEL score ≥ 0.88 (0.921) (PP3).

PM1_Supporting

Variant is within the Runt Homology domain (AA 89-204), but does not affect an established hotspot variant (PM1_supporting).

PM2_Supporting

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

BS4

Segregation data for this variant has not been reported in literature.

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.

BP7

This variant is not a synonymous or intronic variant.

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.

PS2

De novo data for this variant has not been reported in literature.

PS3

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

PS1

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

PP1

Segregation data for this variant has not been reported in literature.

PP2

This rule is not applicable for MM-VCEP.

PP4

This rule is not applicable for MM-VCEP.

PM4

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

PM5

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

PM6

De novo data for this variant has not been reported in literature.

BA1

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

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