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.426T>C (p.Ala142=)

CA10014518

1142251 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: bf93924e-190a-4ede-8345-908491062acc

Approved on: 2022-07-05

Published on: 2022-07-05

HGVS expressions

NM_001754.5:c.426T>C

NM_001754.5(RUNX1):c.426T>C (p.Ala142=)

NC_000021.9:g.34880639A>G

CM000683.2:g.34880639A>G

NC_000021.8:g.36252936A>G

CM000683.1:g.36252936A>G

NC_000021.7:g.35174806A>G

NG_011402.2:g.1109073T>C

ENST00000675419.1:c.426T>C

ENST00000300305.7:c.426T>C

ENST00000344691.8:c.345T>C

ENST00000358356.9:c.345T>C

ENST00000399237.6:c.390T>C

ENST00000399240.5:c.345T>C

ENST00000437180.5:c.426T>C

ENST00000455571.5:c.387T>C

ENST00000482318.5:c.*16T>C

NM_001001890.2:c.345T>C

NM_001122607.1:c.345T>C

NM_001754.4:c.426T>C

NM_001001890.3:c.345T>C

NM_001122607.2:c.345T>C

Likely Benign

BP4 BP7

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

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.426T>C (p.Ala142=) is a synonymous variant therefore REVEL score is not applicable and SpliceAI is ≤0.20 (0.00) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -2.86813 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). In summary, this variant meets the criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and BP7

BP4

Synonymous variant therefore not REVEL score applicable and SpliceAI is ≤0.20 (0.00)

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -2.86813 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7)

BA1

Variant present in gnomAD v2.1.1. and v3.1.2. (MAF 0.0001309, 2/15274 in Latino/and mixed American population) but does not meet criteria for code

BP2

No homozygotes present in gnomAD v2.1.1. or v3.1.2.

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

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BS1

Variant present in gnomAD v2.1.1. and v3.1.2. (MAF 0.0001309, 2/15274 in Latino/and mixed American population) but does not meet criteria for code

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Synonymous variant therefore not REVEL score applicable and SpliceAI is not ≥0.38 (0.00)

PP2

This rule is not applicable for MM-VCEP

PM6

No case studies found

PM2

Variant present in gnomAD v2.1.1. and v3.1.2.

PM5

Not a missense variant

PM1

Not a missense variant

PM3

This rule is not applicable for MM-VCEP

PM4

Not an inframe deletion/insertion

PS4

No case studies found

PS2

No case studies found

PS3

No functional studies found

PS1

The amino acid has not been previously established as pathogenic

PVS1

Not a null variant

Curation History

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