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.1158C>T (p.Pro386=)

CA512341264

1150152 (ClinVar)

Gene: RUNX1 (HGNC:861)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: 3c34fe88-e5c4-44d8-a423-e43acc7a8bab

Approved on: 2024-07-11

Published on: 2024-07-11

HGVS expressions

NM_001754.5(RUNX1):c.1158C>T (p.Pro386=)

NM_001754.5:c.1158C>T

NC_000021.9:g.34792420G>A

CM000683.2:g.34792420G>A

NC_000021.8:g.36164717G>A

CM000683.1:g.36164717G>A

NC_000021.7:g.35086587G>A

NG_011402.2:g.1197292C>T

ENST00000675419.1:c.1158C>T

ENST00000300305.7:c.1158C>T

ENST00000344691.8:c.1077C>T

ENST00000399240.5:c.885C>T

ENST00000437180.5:c.1158C>T

ENST00000482318.5:c.*748C>T

NM_001001890.2:c.1077C>T

NM_001754.4:c.1158C>T

NM_001001890.3:c.1077C>T

Likely Benign

BP7 BP4

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

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.1158C>T (p.Pro386=) is a synonymous variant; therefore, no REVEL score is applicable. SpliceAI score is ≤ 0.20 (0.00) (BP4). Evolutionary conservation algorithms predict the site as not being conserved (PhyloP score -4.82834 < 2.0), or the variant is the reference nucleotide in one primate and/or three mammal species (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -4.82834 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

BP4

Synonymous variant therefore no REVEL score is applicable and SpliceAI is ≤0.20 (0.00) (BP4).

BS2

This rule is not applicable for MM-VCEP

PVS1

Not a null variant

BS4

No case studies found

BS3

No functional studies found

BS1

Variant only present in gnomAD v2.1.1 but does not meet code criteria (MAF 0, 0/10094 in African subpopulation)

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

PS4

Prevalence of variant in affected individuals is not higher than in controls

PS2

No case studies found

PS3

No functional studies found

PS1

Amino acid has not been previously estbalished as pathogenic

BA1

Variant only present in gnomAD v2.1.1 but does not meet code criteria (MAF 0, 0/10094 in African subpopulation)

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Synonymous variant therefore no REVEL score is 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 only present in gnomAD v2.1.1 but does not meet code criteria (MAF 0, 0/10094 in African subpopulation)

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

Curation History

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