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.805+12836A>G

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA14892082

1260410 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dda1735c-9240-46d0-a84c-6a98b2f8cf0b

Approved on: 2024-11-04

Published on: 2024-11-04

HGVS expressions

NM_001754.5:c.805+12836A>G

NM_001754.5(RUNX1):c.805+12836A>G

NC_000021.9:g.34821574T>C

CM000683.2:g.34821574T>C

NC_000021.8:g.36193871T>C

CM000683.1:g.36193871T>C

NC_000021.7:g.35115741T>C

NG_011402.2:g.1168138A>G

ENST00000675419.1:c.805+12836A>G

ENST00000300305.7:c.805+12836A>G

ENST00000344691.8:c.724+12836A>G

ENST00000358356.9:c.*94A>G

ENST00000399240.5:c.533-22112A>G

ENST00000437180.5:c.805+12836A>G

ENST00000479325.1:n.242A>G

ENST00000482318.5:c.*395+12836A>G

NM_001001890.2:c.724+12836A>G

NM_001122607.1:c.*94A>G

NM_001754.4:c.805+12836A>G

NM_001001890.3:c.724+12836A>G

NM_001122607.2:c.*94A>G

Benign

BP7 BP4 BP2 BA1

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

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

The NM_001754.5(RUNX1):c.805+12836A>G variant is a deep intronic variant that is not predicted by SpliceAI to impact splicing (BP4). The variant's highest minor allele frequency (MAF) of 0.9987(99.87%, 1156/1558 alleles) in the East Asian subpopulation of the gnomADv2.1.1 cohort is ≥ 0.0015 (0.15%) (BP1). Additionally this variant is detected in a homozygous state in 777 individuals in a population database (gnomADv2.1.1) (BP2). This deep intronic variant is not well conserved with a phyloP100way score of -0.014 (BP7 ≤2.0). It has not been reported in individuals meeting at least one of the RUNX1 phenotypic criteria. In summary, the clinical significance of this variant is Benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2, BP4, BP7.

BP7

This intronic variant has a SpliceAI score of zero and is not well conserved with a phyloP100way score of -0.014 (BP7 ≤2.0)

BP4

SpliceAI score of 0

BP2

This variant is detected in a homozygous state in 777 individual in a population database (gnomADv2.1.1). (BP2)

BA1

MAF of 0.9987(99.87%, 1156/1558 alleles) in the East Asian subpopulation of the gnomADv2.1.1 cohort is ≥ 0.0015 (0.15%) (BA1).

BP5

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP3

This rule is not applicable for MM-VCEP

PS4

No case study found

PS2

No case study found

PS1

No amino acid change

PS3

No studies found

PP1

No case study found

PP3

Not a missense variant

PP2

This rule is not applicable for MM-VCEP

PP4

This rule is not applicable for MM-VCEP

PM5

not a missense variant

PM1

Not located in known mutational hot spot or established functional domain

PM4

No protein length change is predicted

PM3

This rule is not applicable for MM-VCEP

PM6

No case study found

PM2

BA1 met

PVS1

Not a null variant

BS4

No case study found

BS3

No studies found

BS1

BA1 met

BS2

This rule is not applicable for MM-VCEP

Curation History

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