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.339del (p.Ile114fs)

CA658824421

561235 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: aa00bb05-fdbd-48e3-b409-3cdd4e1692c1

HGVS expressions

NM_001754.5:c.339del

NM_001754.5(RUNX1):c.339del (p.Ile114fs)

NC_000021.9:g.34886857del

CM000683.2:g.34886857del

NC_000021.8:g.36259154del

CM000683.1:g.36259154del

NC_000021.7:g.35181024del

NG_011402.2:g.1102857del

ENST00000675419.1:c.339del

ENST00000300305.7:c.339del

ENST00000344691.8:c.258del

ENST00000358356.9:c.258del

ENST00000399237.6:c.303del

ENST00000399240.5:c.258del

ENST00000437180.5:c.339del

ENST00000455571.5:c.300del

ENST00000482318.5:c.59-6142del

NM_001001890.2:c.258del

NM_001122607.1:c.258del

NM_001754.4:c.339del

NM_001001890.3:c.258del

NM_001122607.2:c.258del

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PM2_Supporting PVS1

PM6 PM5 PM1 PM3 PM4 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP7 BP5 PS4 PS2 PS1 PS3 BA1 PP1 PP4 PP3 PP2

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.339del (p.Ile114fs) is a frameshift variant predicted to undergo NMD (PVS1 SNV tree). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).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: PVS1 and PM2_supporting

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

PVS1

NM_001754.5(RUNX1):c.339del (p.Ile114fs) is a frameshift variant predicted to undergo NMD (PVS1 SNV tree)

PM6

No case studies found

PM5

Amino acid has not been previously established as pathogenic

PM1

Not a missense variant

PM3

This rule is not applicable for MM-VCEP

PM4

This is not an in-frame deletion/insertion that affects at least one of the other residues (AA 89-204) within the RHD

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BS1

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

BP2

Variant not present in gnomAD v2.1.1 or v3.1.2

BP3

This rule is not applicable for MM-VCEP

BP4

Not a missense, synonymous, or intronic variant therefore code does not apply

BP1

This rule is not applicable for MM-VCEP

BP7

Not applicable, not a synonymous or intronic variant

BP5

This rule is not applicable for MM-VCEP

PS4

No case studies found

PS2

No case studies found

PS1

Amino acid has not been previously established as pathogenic

PS3

No functional studies found

BA1

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

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Not a missense, synonymous, or intronic variant therefore code does not apply

PP2

This rule is not applicable for MM-VCEP

Approved on: 2022-07-05

Published on: 2022-07-05

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