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.171_223del (p.Leu58fs)

CA658824423

561229 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dcd0d5ba-7b74-4a9d-b1a7-90dcba1784eb

HGVS expressions

NM_001754.5:c.171_223del

NM_001754.5(RUNX1):c.171_223del (p.Leu58fs)

NC_000021.9:g.34886971_34887023del

CM000683.2:g.34886971_34887023del

NC_000021.8:g.36259268_36259320del

CM000683.1:g.36259268_36259320del

NC_000021.7:g.35181138_35181190del

NG_011402.2:g.1102689_1102741del

ENST00000675419.1:c.171_223del

ENST00000300305.7:c.171_223del

ENST00000344691.8:c.90_142del

ENST00000358356.9:c.90_142del

ENST00000399237.6:c.135_187del

ENST00000399240.5:c.90_142del

ENST00000437180.5:c.171_223del

ENST00000455571.5:c.132_184del

ENST00000482318.5:c.59-6310_59-6258del

NM_001001890.2:c.90_142del

NM_001122607.1:c.90_142del

NM_001754.4:c.171_223del

NM_001001890.3:c.90_142del

NM_001122607.2:c.90_142del

Pathogenic

PM2_Supporting PM5_Supporting PVS1 PS4_Supporting

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

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

The c.171_223del (p.Leu58Profs*62) variant is a frameshift deletion variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). In addition, this variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting), and was identified in a a 65-year-old female tested due to "thrombocytopenia with predisposition to AML" (PS4_supporting; SCV000807767.1). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PS4_supporting, and PM2_supporting.

PM2_Supporting

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

PM5_Supporting

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

PVS1

The c.171_223del (p.Leu58Profs*62) variant is a frameshift deletion variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay.

PS4_Supporting

A 65-year-old female who was testing due to "thrombocytopenia with predisposition to AML" (SCV000807767.1).

PM6

De novo data for this variant has not been reported in literature.

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.

BS2

This rule is not applicable for MM-VCEP.

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS4

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

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

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.

BP5

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

PS1

This variant is not a missense, or synonymous variant.

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS2

De novo data for this variant has not been reported in literature.

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

PP1

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

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.

Approved on: 2024-03-26

Published on: 2024-03-26

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