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.1283dup (p.Leu429fs)

CA16616491

409824 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8fa88b62-804b-4aed-8787-2355874f0563

Approved on: 2024-08-01

Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.1283dup

NM_001754.5(RUNX1):c.1283dup (p.Leu429fs)

NC_000021.9:g.34792295dup

CM000683.2:g.34792295dup

NC_000021.8:g.36164592dup

CM000683.1:g.36164592dup

NC_000021.7:g.35086462dup

NG_011402.2:g.1197417dup

ENST00000675419.1:c.1283dup

ENST00000300305.7:c.1283dup

ENST00000344691.8:c.1202dup

ENST00000399240.5:c.1010dup

ENST00000437180.5:c.1283dup

ENST00000482318.5:c.*873dup

NM_001001890.2:c.1202dup

NM_001754.4:c.1283dup

NM_001001890.3:c.1202dup

Likely Pathogenic

PM5_Supporting PVS1_Strong PS4_Supporting

BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS1 PS2 PS3 BA1 PM3 PM1 PM4 PM6 PM2 PP4 PP1 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:c.1283dup (p.Leu429fs) is a frameshift variant which is not expected to result in nonsense-mediated mRNA decay, but the predicted truncated/altered region is critical to protein function (PVS1_strong). This variant is downstream of c.98 (PM5_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_supporting; SCV000550167.3). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM5_supporting, PM2_supporting, PVS1.

PM5_Supporting

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

PVS1_Strong

Duplication in c.1283 generating a frameshift and a truncated protein. This change is not predicted to undergo NMD.

PS4_Supporting

This variant was reported in 1 proband meeting at least one of the RUNX1-phenotypic criteria in Clinvar (SCV000550167.3).

BS4

Only one proband reported with the variant. No family study for this patient.

BS3

There is no wellestablished in vitro or in vivo functional studies for this variant.

BS1

This variant is absent from gnomAD v2 and v3.

BS2

This rule is not applicable to the MMVCEP.

BP5

This rule is not applicable to the MMVCEP.

BP7

This variant is a frameshift.

BP2

No data.

BP3

This variant is a frameshift.

BP4

This change is not a missense variant.

BP1

This change is not a missense variant.

PS1

This change is a frameshift variant.

PS2

No information.

PS3

There is no wellestablished in vitro or in vivo functional studies for this variant.

BA1

This variant is absent from gnomAD v2 and v3.

PM3

This rule is not applicable to the MMVCEP.

PM1

This change is not a mutational hotspot.

PM4

This variant is a frameshift.

PM6

No information.

PM2

This rule is not applicable to the MMVCEP.

PP4

This rule is not applicable to the MMVCEP.

PP1

Only one proband reported with the variant. No family study for this patient.

PP3

This change is not a missense variant.

PP2

This change is not a missense variant.

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