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.422_423insAACC

CA1139771069

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9b807b63-4df0-4550-998d-e8fc863076fc

HGVS expressions

NM_001754.5:c.422_423insAACC

NC_000021.9:g.34880643_34880644insGTTG

CM000683.2:g.34880643_34880644insGTTG

NC_000021.8:g.36252940_36252941insGTTG

CM000683.1:g.36252940_36252941insGTTG

NC_000021.7:g.35174810_35174811insGTTG

NG_011402.2:g.1109069_1109070insAACC

ENST00000675419.1:c.422_423insAACC

ENST00000300305.7:c.422_423insAACC

ENST00000344691.8:c.341_342insAACC

ENST00000358356.9:c.341_342insAACC

ENST00000399237.6:c.386_387insAACC

ENST00000399240.5:c.341_342insAACC

ENST00000437180.5:c.422_423insAACC

ENST00000455571.5:c.383_384insAACC

ENST00000482318.5:c.*12_*13insAACC

NM_001001890.2:c.341_342insAACC

NM_001122607.1:c.341_342insAACC

NM_001754.4:c.422_423insAACC

NM_001001890.3:c.341_342insAACC

NM_001122607.2:c.341_342insAACC

Pathogenic

PM5_Supporting PVS1 PM2_Supporting

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

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 (+) c.98-c.779 as per VCEP specifications) (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant is a nonsense/frameshift variant 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 Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_Supporting, PM5_supporting, PVS1

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 (+) c.98-c.779 as per VCEP specifications) (PVS1).

PM2_Supporting

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

PS4

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

PS2

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

PS3

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PS1

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

PP1

This variant was not found to co-segregate with disease in 3 or more affected family members in the literature. 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.

BA1

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

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.

BS2

This rule is not applicable for MM-VCEP.

PM3

This rule is not applicable for MM-VCEP.

PM1

This variant is not a missense variant.

PM4

This variant is not an in-frame deletion/insertion.

PM6

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

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for MM-VCEP.

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.

Approved on: 2024-06-24

Published on: 2024-06-24

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