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.442_444dup

CA2830665545

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bf20d336-c8ba-4e59-aee7-46ff32633d17

Approved on: 2024-09-16

Published on: 2024-09-16

HGVS expressions

NM_001754.5:c.442_444dup

NC_000021.9:g.34880621_34880623dup

CM000683.2:g.34880621_34880623dup

NC_000021.8:g.36252918_36252920dup

CM000683.1:g.36252918_36252920dup

NC_000021.7:g.35174788_35174790dup

NG_011402.2:g.1109089_1109091dup

ENST00000675419.1:c.442_444dup

ENST00000300305.7:c.442_444dup

ENST00000344691.8:c.361_363dup

ENST00000358356.9:c.361_363dup

ENST00000399237.6:c.406_408dup

ENST00000399240.5:c.361_363dup

ENST00000437180.5:c.442_444dup

ENST00000455571.5:c.403_405dup

ENST00000482318.5:c.*32_*34dup

NM_001001890.2:c.361_363dup

NM_001122607.1:c.361_363dup

NM_001754.4:c.442_444dup

NM_001001890.3:c.361_363dup

NM_001122607.2:c.361_363dup

Uncertain Significance

PM4_Supporting PM2_Supporting

BP7 BP5 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 PVS1 PP1 PP4 PP3 PP2 PM6 PM1 PM5 PM3 BA1 BS4 BS3 BS1 BS2

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.442_444dup (p.Thr148dup)is an in-frame duplication which occurs in a residue within the Runt Homology Domain, but is not in an established hotspot variant (PM4_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, PM4_supporting.

PM4_Supporting

This in-frame duplication affects at least one of the other residues (AA 89-204) within the RHD (PM4_Supporting).

PM2_Supporting

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

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.

PS2

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

PS4

Proband 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.

PS1

This variant is not a missense variant.

PVS1

This variant is not a null variant.

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.

PM6

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

PM1

This variant is not a missense variant.

PM5

This variant is not a missense variant.

PM3

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

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

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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.