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.133_135del (p.Thr45del)

CA2573157368

1389496 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 026a2ebe-2f31-4778-b597-330e99ca3e4e

Approved on: 2024-07-11

Published on: 2024-07-11

HGVS expressions

NM_001754.5:c.133_135del

NM_001754.5(RUNX1):c.133_135del (p.Thr45del)

NC_000021.9:g.34887061_34887063del

CM000683.2:g.34887061_34887063del

NC_000021.8:g.36259358_36259360del

CM000683.1:g.36259358_36259360del

NC_000021.7:g.35181228_35181230del

NG_011402.2:g.1102651_1102653del

ENST00000675419.1:c.133_135del

ENST00000300305.7:c.133_135del

ENST00000344691.8:c.52_54del

ENST00000358356.9:c.52_54del

ENST00000399237.6:c.97_99del

ENST00000399240.5:c.52_54del

ENST00000437180.5:c.133_135del

ENST00000455571.5:c.94_96del

ENST00000475045.6:c.133_135del

ENST00000482318.5:c.59-6348_59-6346del

NM_001001890.2:c.52_54del

NM_001122607.1:c.52_54del

NM_001754.4:c.133_135del

NM_001001890.3:c.52_54del

NM_001122607.2:c.52_54del

Uncertain Significance

PM2_Supporting

PS2 PS4 PS3 PS1 PVS1 PP1 PP4 PP3 PP2 PM6 PM1 PM5 PM3 PM4 BA1 BS4 BS3 BS1 BS2 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

NM_001754.5(RUNX1):c.133_135del (p.Thr45del) is an inframe deletion which does not affect a known functional domain. 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.

PM2_Supporting

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

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

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

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 does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.

PM5

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

PM3

This rule is not applicable for MM-VCEP.

PM4

This in-frame deletion/insertion does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.

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.

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.

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