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.426T>C (p.Ala142=)

CA10014518

1142251 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

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

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

BP7 BP4

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

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)

BP4

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

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

BP5

This rule is not applicable for MM-VCEP

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

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

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

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

PVS1

Not a null variant

PM6

No case studies found

PM2

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

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

Approved on: 2022-07-05

Published on: 2022-07-05

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