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.253_254insGGGG (p.His85fs)

CA2499225882

1073521 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dbb058ec-2615-42fd-90aa-2d3f4ed0b482

HGVS expressions

NM_001754.5:c.253_254insGGGG

NM_001754.5(RUNX1):c.253_254insGGGG (p.His85fs)

NC_000021.9:g.34886940_34886941insCCCC

CM000683.2:g.34886940_34886941insCCCC

NC_000021.8:g.36259237_36259238insCCCC

CM000683.1:g.36259237_36259238insCCCC

NC_000021.7:g.35181107_35181108insCCCC

NG_011402.2:g.1102771_1102772insGGGG

ENST00000675419.1:c.253_254insGGGG

ENST00000300305.7:c.253_254insGGGG

ENST00000344691.8:c.172_173insGGGG

ENST00000358356.9:c.172_173insGGGG

ENST00000399237.6:c.217_218insGGGG

ENST00000399240.5:c.172_173insGGGG

ENST00000437180.5:c.253_254insGGGG

ENST00000455571.5:c.214_215insGGGG

ENST00000482318.5:c.59-6228_59-6227insGGGG

NM_001001890.2:c.172_173insGGGG

NM_001122607.1:c.172_173insGGGG

NM_001754.4:c.253_254insGGGG

NM_001001890.3:c.172_173insGGGG

NM_001122607.2:c.172_173insGGGG

Likely Pathogenic

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

PVS1 PM2_Supporting

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

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.253_254insGGGG (p.His85fs) 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

PVS1

NM_001754.5(RUNX1):c.253_254insGGGG (p.His85fs) is a frameshift variant predicted to undergo NMD (PVS1, SNV tree)

PM2_Supporting

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

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 (PM2).

BP2

No homozygotes present in gnomAD v2.1.1 and v3.1.2

BP3

This rule is not applicable for MM-VCEP

BP4

Not a missense, synonymous, or intronic variant

BP1

This rule is not applicable for MM-VCEP

BP7

Not a missense, synonymous, or intronic variant

BP5

This rule is not applicable for MM-VCEP

PS2

No case studies found

PS4

No case studies found

PS3

No functional studies found

PS1

The amino acid has not been previously established as a pathogenic variant by MMVCEP

BA1

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

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Not a missense, synonymous, or intronic variant

PP2

This rule is not applicable for MM-VCEP

PM5

Not a missense variant

PM1

Not located in a mutational hotspot or critical area

PM3

This rule is not applicable for MM-VCEP

PM4

The variant does not result in an in-frame deletion/ insertion in a non-repeat region and is not a stop-loss variant

PM6

No case studies found

Approved on: 2022-03-21

Published on: 2022-07-05

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