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.1098C>T (p.Ile366=)

CA10014203

1129441 (ClinVar)

Gene: RUNX1 (HGNC:861)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: deb5fbf1-e5eb-46a5-b1f6-ccaa7def24fd

Approved on: 2022-03-08

Published on: 2022-07-05

HGVS expressions

NM_001754.5:c.1098C>T

NM_001754.5(RUNX1):c.1098C>T (p.Ile366=)

NC_000021.9:g.34792480G>A

CM000683.2:g.34792480G>A

NC_000021.8:g.36164777G>A

CM000683.1:g.36164777G>A

NC_000021.7:g.35086647G>A

NG_011402.2:g.1197232C>T

ENST00000675419.1:c.1098C>T

ENST00000300305.7:c.1098C>T

ENST00000344691.8:c.1017C>T

ENST00000399240.5:c.825C>T

ENST00000437180.5:c.1098C>T

ENST00000482318.5:c.*688C>T

NM_001001890.2:c.1017C>T

NM_001754.4:c.1098C>T

NM_001001890.3:c.1017C>T

Likely Benign

BP4 BP7

PS4 PS2 PS3 PS1 BP3 BP2 BP1 BP5 PP1 PP4 PP3 PP2 BA1 PM5 PM4 PM1 PM3 PM6 PM2 BS2 BS4 BS3 BS1 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.1098C>T (p.Ile366=) is a synonymous variant therefore no REVEL score and SpliceAI is ≤0.20 (0.00) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.378488 < 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 and BP7

BP4

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

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.378488 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

PS4

No case studies found

PS2

no case studies found

PS3

No functional studies found

PS1

Amino acid has not been previously established as pathogenic

BP3

This rule is not applicable for MM-VCEP

BP2

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

BP1

This rule is not applicable for MM-VCEP

BP5

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 no REVEL score and SpliceAI is NOT ≥0.38 (0.00)

PP2

This rule is not applicable for MM-VCEP

BA1

Present in gnomAD v2.1.1 and v3.1.2 but does not meet criteria for code

PM5

Not a missense variant

PM4

Not an inframe deletion/insertion

PM1

Not a missense variant

PM3

This rule is not applicable for MM-VCEP

PM6

No case studies found

PM2

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

Present in gnomAD v2.1.1 and v3.1.2 but does not meet criteria for code

PVS1

Not a null variant

Curation History

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