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.369T>A (p.Asp123Glu)

CA10014523

463993 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 06a1ff67-da9f-4444-97c5-9cb9f8713049

Approved on: 2023-11-13

Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.369T>A

NM_001754.5(RUNX1):c.369T>A (p.Asp123Glu)

NC_000021.9:g.34880696A>T

CM000683.2:g.34880696A>T

NC_000021.8:g.36252993A>T

CM000683.1:g.36252993A>T

NC_000021.7:g.35174863A>T

NG_011402.2:g.1109016T>A

ENST00000675419.1:c.369T>A

ENST00000300305.7:c.369T>A

ENST00000344691.8:c.288T>A

ENST00000358356.9:c.288T>A

ENST00000399237.6:c.333T>A

ENST00000399240.5:c.288T>A

ENST00000437180.5:c.369T>A

ENST00000455571.5:c.330T>A

ENST00000482318.5:c.76T>A

NM_001001890.2:c.288T>A

NM_001122607.1:c.288T>A

NM_001754.4:c.369T>A

NM_001001890.3:c.288T>A

NM_001122607.2:c.288T>A

Likely Benign

BP7 BP4 PM1_Supporting

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

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

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, BP7, PM1_Supporting

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -2.40< 2.0)

BP4

This missense variant has a REVEL score ≤0.50 (0.325) and a SpliceAI score ≤ 0.20 (Acceptor Loss 0.00).

PM1_Supporting

This variant affects one of the other residues (AA 89-204) within the RHD

BP5

This rule is not applicable for the MM-VCEP

PVS1

This variant is not a null variant, as it does not impact any of the following processes or sites: Nonsense, frameshift, canonical +/- 1 or 2 splice sites, initiation codon, single exon deletion, multiple exon deletions

BP2

This variant has not been detected in a homozygous state in an individual or in a population database (gnomAD).

BP3

This rule is not applicable for the MM-VCEP

BP1

This rule is not applicable for the MM-VCEP

PS2

This variant has not been found to co-segregate with the disease in the literature.

PS4

This variant has not been reported in probands.

PS3

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PS1

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

PP1

This variant was not found to co-segregate with disease in multiple affected family members.

PP4

This rule is not applicable for the MM-VCEP

PP3

This missense variant does not have a REVEL score of ≥ 0.88 (0.325) nor does it impactfully alter a splice site (Splice AI Acceptor Loss 0.0).

PP2

This rule is not applicable for the MM-VCEP

PM6

This variant has not been reported in probands in the literature.

PM2

Variant is present at at 0.00009(0.009%, 3/34580,) in the Latino subpopulation of gnomAD 2 cohort

PM5

Though other missense changes have been found at this location, non have been determined to be pathogenic yet.

PM3

This rule is not applicable for the MM-VCEP

PM4

This variant is not an inframe indel.

BA1

Highest MAF is less than 0.0015 (0.15%) at 0.00009(0.009%, 3/34580,) in the Latino subpopulation of gnomAD 2 cohort

BS2

This rule is not applicable for the MM-VCEP

BS4

This variant has not been reported in affected family members.

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

BS1

Highest MAF is less than 0.00015 (0.015%) at 0.00009(0.009%, 3/34580,) in the Latino subpopulation of gnomAD 2 cohort

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.