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.259_260dup (p.Glu88fs)

CA2573157362

1692643 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 533ef322-1977-4755-abd1-f95c0dbb33ad

HGVS expressions

NM_001754.5:c.259_260dup

NM_001754.5(RUNX1):c.259_260dup (p.Glu88fs)

NC_000021.9:g.34886935_34886936dup

CM000683.2:g.34886935_34886936dup

NC_000021.8:g.36259232_36259233dup

CM000683.1:g.36259232_36259233dup

NC_000021.7:g.35181102_35181103dup

NG_011402.2:g.1102777_1102778dup

ENST00000675419.1:c.259_260dup

ENST00000300305.7:c.259_260dup

ENST00000344691.8:c.178_179dup

ENST00000358356.9:c.178_179dup

ENST00000399237.6:c.223_224dup

ENST00000399240.5:c.178_179dup

ENST00000437180.5:c.259_260dup

ENST00000455571.5:c.220_221dup

ENST00000482318.5:c.59-6222_59-6221dup

NM_001001890.2:c.178_179dup

NM_001122607.1:c.178_179dup

NM_001754.4:c.259_260dup

NM_001001890.3:c.178_179dup

NM_001122607.2:c.178_179dup

Pathogenic

PVS1 PM2_Supporting PM5_Supporting

PS4 PS2 PS1 PS3 PM1 PM4 PM3 PM6 BA1 BP3 BP2 BP4 BP1 BP7 BP5 BS2 BS4 BS3 BS1 PP4 PP3 PP2 PP1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The NM_001754.5(RUNX1):c.259_260dup (p.Glu88AlafsTer?) is a null variant that affects all biologically relevant transcripts (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). The variant Impacts the 88th amino acid just outside the RHD domain (PM4_supporting applied to amino acid residues 89-204 within the RHD). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). 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.

PVS1

The NM_001754.5(RUNX1):c.259_260dup (p.Glu88AlafsTer?) null variant affects all biologically relevant transcripts.

PM2_Supporting

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

PM5_Supporting

This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting).

PS4

No case study found

PS2

No case study found

PS1

This amino acid has not been established as pathogenic previously

PS3

No case study found

PM1

Amino acid 88 is outside the hot spot range as defined by the MM-VCEP

PM4

Impacts the 88th amino acid just outside the RHD domain (PM$_supporting applied to amino acid residues 89-204 within the RHD)

PM3

This rule is not applicable for MM-VCEP

PM6

No case study found

BA1

PM2 Met

BP3

This rule is not applicable for MM-VCEP

BP2

No case study found

BP4

Null variant

BP1

This rule is not applicable for MM-VCEP

BP7

Null variant

BP5

This rule is not applicable for MM-VCEP

BS2

This rule is not applicable for MM-VCEP

BS4

No case study found

BS3

No case study found

BS1

PM2 Met

PP4

This rule is not applicable for MM-VCEP

PP3

Null variant

PP2

This rule is not applicable for MM-VCEP

PP1

No case study found

Approved on: 2023-12-09

Published on: 2023-12-09

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