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.98-21T>C

CA10014594

1319385 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3a132aaa-d2d8-4be9-9d7d-da84476415e0

Approved on: 2024-09-18

Published on: 2024-09-18

HGVS expressions

NM_001754.5:c.98-21T>C

NM_001754.5(RUNX1):c.98-21T>C

NC_000021.9:g.34887117A>G

CM000683.2:g.34887117A>G

NC_000021.8:g.36259414A>G

CM000683.1:g.36259414A>G

NC_000021.7:g.35181284A>G

NG_011402.2:g.1102595T>C

ENST00000675419.1:c.98-21T>C

ENST00000300305.7:c.98-21T>C

ENST00000344691.8:c.-5T>C

ENST00000358356.9:c.-5T>C

ENST00000399237.6:c.62-21T>C

ENST00000399240.5:c.-5T>C

ENST00000437180.5:c.98-21T>C

ENST00000455571.5:c.59-21T>C

ENST00000475045.6:c.98-21T>C

ENST00000482318.5:c.59-6404T>C

NM_001001890.2:c.-5T>C

NM_001122607.1:c.-5T>C

NM_001754.4:c.98-21T>C

NM_001001890.3:c.-5T>C

NM_001122607.2:c.-5T>C

Likely Benign

BS1

BA1 BP7 BP5 BP2 BP3 BP4 BP1 BS4 BS3 BS2 PP1 PP4 PP3 PP2 PS2 PS4 PS3 PS1 PM1 PM5 PM3 PM4 PVS1 PM6 PM2

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.98-21T>C is an intronic variant. This variant has a MAF of 0.0002794 (0.028%, 19/67998, 19 alleles) in the European (non-Finnish) subpopulation of the gnomAD v3.1.2 cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This variant may impact splicing (Splice AI: Acceptor Loss Score = 0.35). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1.

BS1

MAF of 0.0002794 (0.028%, 19/67998, 19 alleles) in the European (non-Finnish) subpopulation of the gnomAD v3.1.2 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1).

BA1

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

BP7

This variant does not have a phyloP score < 2.0 or a SpliceAI score ≤ 0.20.

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 synonymous or intronic variant does not have a SpliceAI score ≤ 0.20.

BP1

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.

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 synonymous or intronic variant does not have a REVEL score ≥ 0.88 or a SpliceAI score ≥ 0.38.

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.

PM4

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

PVS1

This variant is not a null variant.

PM6

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

PM2

This variant is present in at least one population database.

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