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.385_395del (p.Leu129fs)

CA2580098648

2092471 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2714a8bd-0723-4a2e-b00a-8527d6936038

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.385_395del

NM_001754.5(RUNX1):c.385_395del (p.Leu129fs)

NC_000021.9:g.34880671_34880681del

CM000683.2:g.34880671_34880681del

NC_000021.8:g.36252968_36252978del

CM000683.1:g.36252968_36252978del

NC_000021.7:g.35174838_35174848del

NG_011402.2:g.1109032_1109042del

ENST00000675419.1:c.385_395del

ENST00000300305.7:c.385_395del

ENST00000344691.8:c.304_314del

ENST00000358356.9:c.304_314del

ENST00000399237.6:c.349_359del

ENST00000399240.5:c.304_314del

ENST00000437180.5:c.385_395del

ENST00000455571.5:c.346_356del

ENST00000482318.5:c.92_102del

NM_001001890.2:c.304_314del

NM_001122607.1:c.304_314del

NM_001754.4:c.385_395del

NM_001001890.3:c.304_314del

NM_001122607.2:c.304_314del

Likely Pathogenic

PM5_Supporting PVS1_Strong PM2_Supporting

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

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.385_395del (p.Leu129AspfsTer5) is a frameshift variant that occurs which terminates 5 amino acids downstream and is predicted to undergo NMD (As per modified RUNX1 PVS1 decision tree ) (PVS1_Strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a frameshift variant that is downstream of c.98 (PM5_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_strong, PM2_supporting, PM5_supporting.

PM5_Supporting

Nonsense variant is located downstream of c.98 (in transcript NM_001754.4).

PVS1_Strong

As per modified RUNX1 PVS1 decision tree

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

PS4

No proband has been reported meeting RUNX1 FPD-MM phenotypic criteria

PS2

No case study found

PS1

PM5 met

PS3

No functional studies found

PP1

No case study found

PP4

This rule is not applicable for MM-VCEP

PP3

This is a null variant

PP2

This rule is not applicable for MM-VCEP

PM6

No case study found

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM3

This rule is not applicable for MM-VCEP

PM4

nonsense variant

BA1

PM2_Supporting met

BS4

No case study found

BS3

No functional studies found

BS1

PM2_Supporting met

BS2

This rule is not applicable for MM-VCEP

BP7

No splice affect predicted

BP5

This rule is not applicable for MM-VCEP

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP4

This is a null variant

BP1

This rule is not applicable for MM-VCEP

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