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:c.423_424insAACC

CA1139771060

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fa99d02a-c314-4a29-8e0d-c56e2c5d3a63

HGVS expressions

NM_001754.5:c.423_424insAACC

NC_000021.9:g.34880641_34880642insGGTT

CM000683.2:g.34880641_34880642insGGTT

NC_000021.8:g.36252938_36252939insGGTT

CM000683.1:g.36252938_36252939insGGTT

NC_000021.7:g.35174808_35174809insGGTT

NG_011402.2:g.1109070_1109071insAACC

ENST00000675419.1:c.423_424insAACC

ENST00000300305.7:c.423_424insAACC

ENST00000344691.8:c.342_343insAACC

ENST00000358356.9:c.342_343insAACC

ENST00000399237.6:c.387_388insAACC

ENST00000399240.5:c.342_343insAACC

ENST00000437180.5:c.423_424insAACC

ENST00000455571.5:c.384_385insAACC

ENST00000482318.5:c.*13_*14insAACC

NM_001001890.2:c.342_343insAACC

NM_001122607.1:c.342_343insAACC

NM_001754.4:c.423_424insAACC

NM_001001890.3:c.342_343insAACC

NM_001122607.2:c.342_343insAACC

Pathogenic

PM2_Supporting PM5_Supporting PVS1

PM6 PM3 PM1 PM4 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS4 PS1 PS2 PS3 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

This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (+)/nonsense c.98-c.779 as per VCEP specifications) (PVS1). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). 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 pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM5_supporting 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

This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (+)/nonsense c.98-c.779 as per VCEP specifications) (PVS1).

PM6

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

PM3

This rule is not applicable for the MM-VCEP.

PM1

This variant is not a missense variant.

PM4

This insertion results in a disruption of the reading frame.

BS2

This rule is not applicable for the MM-VCEP.

BS4

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

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

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 insertion results in a disruption of the reading frame.

BP4

This is not a missense variant.

BP1

This is not a missense variant.

BP5

This rule is not applicable for the MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

PS4

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

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

PS2

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

PS3

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

PP3

This is not a missense variant.

PP2

This rule is not applicable for the MM-VCEP.

Approved on: 2024-06-24

Published on: 2024-06-24

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