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.331_336del

CA2830665544

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bce07a41-86ad-4d7f-97be-08fd66313017

Approved on: 2024-09-12

Published on: 2024-09-12

HGVS expressions

NM_001754.5:c.331_336del

NC_000021.9:g.34886859_34886864del

CM000683.2:g.34886859_34886864del

NC_000021.8:g.36259156_36259161del

CM000683.1:g.36259156_36259161del

NC_000021.7:g.35181026_35181031del

NG_011402.2:g.1102849_1102854del

ENST00000675419.1:c.331_336del

ENST00000300305.7:c.331_336del

ENST00000344691.8:c.250_255del

ENST00000358356.9:c.250_255del

ENST00000399237.6:c.295_300del

ENST00000399240.5:c.250_255del

ENST00000437180.5:c.331_336del

ENST00000455571.5:c.292_297del

ENST00000482318.5:c.59-6150_59-6145del

NM_001001890.2:c.250_255del

NM_001122607.1:c.250_255del

NM_001754.4:c.331_336del

NM_001001890.3:c.250_255del

NM_001122607.2:c.250_255del

Uncertain Significance

PM4_Supporting PM2_Supporting

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

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.331_336del (p.Thr111_Leu112del) is an in-frame deletion which affects residues within the Runt Homology Domain, but not an established hotspot residue (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 deletion 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).

BA1

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

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.

BP4

This variant does not have applicable in-silico data available.

BP1

This rule is not applicable for MM-VCEP.

BP3

This rule is not applicable for MM-VCEP.

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.

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.

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.

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.

PVS1

This variant is not a null variant.

PM6

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

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