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.140_150del (p.Leu47fs)

CA2499225885

1069299 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 904ae4b6-8618-46a6-b6be-5e2175941e0d

HGVS expressions

NM_001754.5:c.140_150del

NM_001754.5(RUNX1):c.140_150del (p.Leu47fs)

NC_000021.9:g.34887046_34887056del

CM000683.2:g.34887046_34887056del

NC_000021.8:g.36259343_36259353del

CM000683.1:g.36259343_36259353del

NC_000021.7:g.35181213_35181223del

NG_011402.2:g.1102658_1102668del

ENST00000675419.1:c.140_150del

ENST00000300305.7:c.140_150del

ENST00000344691.8:c.59_69del

ENST00000358356.9:c.59_69del

ENST00000399237.6:c.104_114del

ENST00000399240.5:c.59_69del

ENST00000437180.5:c.140_150del

ENST00000455571.5:c.101_111del

ENST00000482318.5:c.59-6341_59-6331del

NM_001001890.2:c.59_69del

NM_001122607.1:c.59_69del

NM_001754.4:c.140_150del

NM_001001890.3:c.59_69del

NM_001122607.2:c.59_69del

Pathogenic

PVS1 PM2_Supporting PM5_Supporting

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

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.140_150del (p.Leu47fs) is a frameshift variant that is predicted to undergo nonsense mediated decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). Frameshift variant downstream of c.98 (in transcript NM_001754.5) (PM5_supporting). In summary, this variant meets 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 and PM5_supporting.

PVS1

Frameshift variant that is predicted to undergo non sense mediated decay (PVS1)

PM2_Supporting

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

PM5_Supporting

Frameshift variant downstream of c.98 (in transcript NM_001754.4) (PM5_supporting).

PS2

No case studies found

PS4

No case studies found

PS3

No functional studies

PS1

Amino acid has not been established as pathogenic by the MMVCEP

PM3

This rule is not applicable for MM-VCEP

PM1

Not a missense variant

PM4

Not an inframe insertion/deletion

PM6

No case studies found

BA1

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

BP2

No homozygotes seen in gnomAD

BP3

This rule is not applicable for MM-VCEP

BP4

Not a missense, synonymous, and intronic variant

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BP7

Not a synonymous or intronic variant

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies

BS1

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

PP1

No case studies found

PP3

Not a missense, synonymous, and intronic variant

PP2

This rule is not applicable for MM-VCEP

PP4

This rule is not applicable for MM-VCEP

Approved on: 2022-07-05

Published on: 2022-07-05

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