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.509-281G>T

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA15984361

1283817 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 18ce521d-9d81-47c8-845e-60157d815093

Approved on: 2025-01-15

Published on: 2025-01-15

HGVS expressions

NM_001754.5:c.509-281G>T

NM_001754.5(RUNX1):c.509-281G>T

NC_000021.9:g.34859859C>A

CM000683.2:g.34859859C>A

NC_000021.8:g.36232156C>A

CM000683.1:g.36232156C>A

NC_000021.7:g.35154026C>A

NG_011402.2:g.1129853G>T

ENST00000675419.1:c.509-281G>T

ENST00000300305.7:c.509-281G>T

ENST00000344691.8:c.428-281G>T

ENST00000358356.9:c.428-281G>T

ENST00000399237.6:c.473-281G>T

ENST00000399240.5:c.428-281G>T

ENST00000437180.5:c.509-281G>T

ENST00000482318.5:c.*99-281G>T

NM_001001890.2:c.428-281G>T

NM_001122607.1:c.428-281G>T

NM_001754.4:c.509-281G>T

NM_001001890.3:c.428-281G>T

NM_001122607.2:c.428-281G>T

Benign

BP2 BP4 BP7 BA1

PM1 PM5 PM3 PM4 PM6 PM2 BS2 BS4 BS3 BS1 BP3 BP1 BP5 PVS1 PS2 PS4 PS3 PS1 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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.509-281G>T is an intronic variant which has a MAF of 0.8530 (85.3%, 35321/41406, 35321 alleles) in the African/African American subpopulation of the gnomAD 3.1.2 cohort which is ≥ 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in 15115 individuals in a population database (gnomAD 3.1.2) (BP2). This intronic variant has a SpliceAI score ≤ 0.20 (0.0) (BP4). This variant has a SpliceAI score ≤ 0.20 (0.0) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-0.45) (BP7). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2, BP4, BP7.

BP2

This variant is detected in a homozygous state in 15115 individuals in a population database (gnomAD 3.1.2) (BP2).

BP4

This intronic variant has a SpliceAI score ≤ 0.20 (0.0) (BP4).

BP7

This variant has a SpliceAI score ≤ 0.20 (0.0) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-0.45) (BP7).

BA1

MAF of 0.8530 (85.3%, 35321/41406, 35321 alleles) in the African/African American subpopulation of the gnomAD 3.1.2 cohort is ≥ 0.0015 (0.15%) (BA1).

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.

PM6

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

PM2

BA1 applied

BS2

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.

BS1

BA1 applied

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

BP5

This rule is not applicable for MM-VCEP.

PVS1

This variant is not a null variant.

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.

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.

Curation History

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.