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.938T>G (p.Leu313Arg)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA10014265

239058 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: af528462-1b7b-4906-9131-a7c90950a02e

Approved on: 2025-01-15

Published on: 2025-01-15

HGVS expressions

NM_001754.5:c.938T>G

NM_001754.5(RUNX1):c.938T>G (p.Leu313Arg)

NC_000021.9:g.34799330A>C

CM000683.2:g.34799330A>C

NC_000021.8:g.36171627A>C

CM000683.1:g.36171627A>C

NC_000021.7:g.35093497A>C

NG_011402.2:g.1190382T>G

ENST00000675419.1:c.938T>G

ENST00000300305.7:c.938T>G

ENST00000344691.8:c.857T>G

ENST00000399240.5:c.665T>G

ENST00000437180.5:c.938T>G

ENST00000482318.5:c.*528T>G

NM_001001890.2:c.857T>G

NM_001754.4:c.938T>G

NM_001001890.3:c.857T>G

Uncertain Significance

BP4

BP2 BP3 BP1 BP7 BP5 PS2 PS4 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM1 PM5 PM3 PM4 PM6 PM2 BS2 PVS1 BS4 BS3 BS1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.938T>G (p.Leu313Arg) is a missense variant. This missense variant has a REVEL score <0.50 (0.202) (BP4) and SpliceAI ≤0.20 (0.01 -29bp Donor Gain). 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: BP4.

BP4

This missense variant has a REVEL score <0.50 (0.202).

BP2

No published cases identified.

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

BP7

This is a missense variant and BP7 does not apply.

BP5

This rule is not applicable for MM-VCEP.

PS2

No published cases identified.

PS4

No published cases identified.

PS3

No published data identified.

PS1

No previously established pathogenic variant identified.

BA1

This variant has a allele frequency of 0.000007072 in gnomAD v2.1.1 (21-36171627-A-C, 2 alleles in African/African American population with mean depth >30) and allele frequency of 0.00001972 in gnomAD v3.1.2 (21-34799330-A-C, 3 alleles in African/African American population with mean depth >30).

PP1

No published cases identified.

PP4

This rule is not applicable for MM-VCEP.

PP3

This variant has a REVEL score of 0.202, is not in the 3 bases preceding a donor splice site or 3 bases following an acceptor splice site, and has a SpliceAI score of <0.20 (Donor Gain score of 0.01 at -29 bp).

PP2

This rule is not applicable for MM-VCEP.

PM1

This variant affects amino acid Leu313 and is not a residue of interest as per MM-VCEP.

PM5

No published data identified.

PM3

This rule is not applicable for MM-VCEP.

PM4

This is a missense variant not predicted to affect splicing or protein length.

PM6

No published cases identified.

PM2

BS2

This rule is not applicable for MM-VCEP.

PVS1

Missense variant not predicted to alter transcription or splice site.

BS4

No published cases identified.

BS3

No published data identified.

BS1

Curation History

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