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]

Variant: NM_001754.5(RUNX1):c.411dup (p.Glu138Ter)

CA2739267616

2820865 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: 3a6bb6cb-0628-40cf-bc39-2f4f9ade5014

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.411dup

NM_001754.5(RUNX1):c.411dup (p.Glu138Ter)

NC_000021.9:g.34880654dup

CM000683.2:g.34880654dup

NC_000021.8:g.36252951dup

CM000683.1:g.36252951dup

NC_000021.7:g.35174821dup

NG_011402.2:g.1109058dup

ENST00000675419.1:c.411dup

ENST00000300305.7:c.411dup

ENST00000344691.8:c.330dup

ENST00000358356.9:c.330dup

ENST00000399237.6:c.375dup

ENST00000399240.5:c.330dup

ENST00000437180.5:c.411dup

ENST00000455571.5:c.372dup

ENST00000482318.5:c.*1dup

NM_001001890.2:c.330dup

NM_001122607.1:c.330dup

NM_001754.4:c.411dup

NM_001001890.3:c.330dup

NM_001122607.2:c.330dup

Pathogenic

PM1_Supporting PM5 PVS1 PM2_Supporting

PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 BA1 BS2 PM6 PM3 PM4 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7

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.411dup (p.Glu138Ter) is a nonsense variant which is predicted to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). It is downstream of c.98 (PM5_Supporting) and impacts amino acid 138, which is located within the Runt Homology Domain (RHD) but does not occur in an established hotspot residue (PM1_Supporting). Clinical and functional data are not available for this variant. In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_Supporting, PM5_Supporting, PM1_Supporting.

PM1_Supporting

This variant is located between AAs 89-204 and is within the RHD.

PM5

This is a nonsense/frameshift variant that is downstream of c.98.

PVS1

This variant is a nonsense variant and is predicted to undergo NMD.

PM2_Supporting

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

PS2

De novo data is not available for this variant.

PS4

Proband data is not available for this variant.

PS3

Functional studies for this variant are not available.

PS1

Pathogenic variants have not been reported at this AA.

PP4

This rule is not applicable for MM-VCEP

PP1

Segregation data is not available for this variant.

PP3

This is not a missense variant

PP2

This rule is not applicable for MM-VCEP

BA1

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

BS2

This rule is not applicable for the MM-VCEP.

PM6

De novo data is not available for this variant.

PM3

This rule is not applicable for MM-VCEP

PM4

This is not an in-frame deletion/insertion.

BS4

Segregation data is not available for this variant.

BS3

Functional studies for this variant are not available.

BS1

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

BP2

This variant has not been reported.

BP3

This is not an in-frame deletion/insertion.

BP4

This is not a missense variant

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BP7

This is not a silent or intronic variant

Curation History

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