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.311del (p.Thr104fs)

CA2695201453

2635335 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 71b75ed7-2118-4691-b808-8713fec1bd56

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.311del

NM_001754.5(RUNX1):c.311del (p.Thr104fs)

NC_000021.9:g.34886883del

CM000683.2:g.34886883del

NC_000021.8:g.36259180del

CM000683.1:g.36259180del

NC_000021.7:g.35181050del

NG_011402.2:g.1102829del

ENST00000675419.1:c.311del

ENST00000300305.7:c.311del

ENST00000344691.8:c.230del

ENST00000358356.9:c.230del

ENST00000399237.6:c.275del

ENST00000399240.5:c.230del

ENST00000437180.5:c.311del

ENST00000455571.5:c.272del

ENST00000482318.5:c.59-6170del

NM_001001890.2:c.230del

NM_001122607.1:c.230del

NM_001754.4:c.311del

NM_001001890.3:c.230del

NM_001122607.2:c.230del

Pathogenic

PM2_Supporting PVS1 PM5_Supporting

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

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.311del (p.Thr104SerfsTer18)is a frameshift variant which terminates 18 amino acids downstream and is predicted to undergo nonsense-mediated decay (as per the modified RUNX1 PVS1 decision tree) (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). It is a frameshift variant that is downstream of c.98 (PM5_Supporting). In summary, this variant meets the 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.

PM2_Supporting

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

PVS1

NM_001754.5(RUNX1):c.311del (p.Thr104SerfsTer18) is a frameshift variant that terminates 18 amino acids downstream and is predicted to undergo nonsense-mediated decay (As per modified RUNX1 PVS1 decision tree ) (PVS1).

PM5_Supporting

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

BS4

No case study found

BS3

No study found

BS1

PM2_Supporting met

BS2

This rule is not applicable for MM-VCEP

BP7

This variant is not a synonymous or intronic variant.

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 variant does not have applicable in-silico data available.

BP1

This rule is not applicable for MM-VCEP

PS4

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

PS2

No case study found

PS1

This variant is not a missense variant.

PS3

No study found

BA1

PM2_Supporting met

PP1

No case study found

PP4

This rule is not applicable for MM-VCEP

PP3

This variant does not have applicable in-silico data available.

PP2

This rule is not applicable for MM-VCEP

PM1

This variant is not a missense variant.

PM3

This rule is not applicable for MM-VCEP

PM4

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

PM6

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

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