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]

Variant: NM_001754.5(RUNX1):c.-9_14dup (p.Ser5fs)

CA3054205290

3642848 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: ecfbc170-8d57-4ab1-98a7-cd85ecbf25f8

Approved on: 2025-05-02

Published on: 2025-05-02

HGVS expressions

NM_001754.5:c.-9_14dup

NM_001754.5(RUNX1):c.-9_14dup (p.Ser5fs)

NC_000021.9:g.35048889_35048911dup

CM000683.2:g.35048889_35048911dup

NC_000021.8:g.36421186_36421208dup

CM000683.1:g.36421186_36421208dup

NC_000021.7:g.35343056_35343078dup

NG_011402.2:g.940804_940826dup

ENST00000675419.1:c.-9_14dup

ENST00000300305.7:c.-9_14dup

ENST00000416754.1:c.-9_14dup

ENST00000437180.5:c.-9_14dup

ENST00000455571.5:c.-9_14dup

ENST00000475045.6:c.-9_14dup

ENST00000482318.5:c.-9_14dup

NM_001754.4:c.-9_14dup

Uncertain Significance

PM2_Supporting

BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP3 BP4 BP1 PM6 PS2 PS4 PS3 PS1 PM1 PM5 PM3 PM4 PVS1 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

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Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.-9_14dup (p.Ser5ArgfsTer22) is a frameshift variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is in an exon that is absent from RUNX1 isoform a and b (c.1-c.97 as per VCEP specifications) (PVS1_NA). 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).

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.

PM6

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

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 a frameshift variant that is NOT downstream of c.98.

PM3

This rule is not applicable for MM-VCEP.

PM4

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

PVS1

This variant is in an exon that is absent from RUNX1 isoform a and b (c.1-c.97 as per VCEP specifications) (PVS1_NA).

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 MM-VCEP.

PP3

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

PP2

This rule is not applicable for MM-VCEP.

Curation History

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