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.1119G>C (p.Ser373=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014198

532687 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8012655d-745f-4e5d-a0a7-2baca88f0e2e

Approved on: 2022-02-11

Published on: 2022-06-30

HGVS expressions

NM_001754.5:c.1119G>C

NM_001754.5(RUNX1):c.1119G>C (p.Ser373=)

NC_000021.9:g.34792459C>G

CM000683.2:g.34792459C>G

NC_000021.8:g.36164756C>G

CM000683.1:g.36164756C>G

NC_000021.7:g.35086626C>G

NG_011402.2:g.1197253G>C

ENST00000675419.1:c.1119G>C

ENST00000300305.7:c.1119G>C

ENST00000344691.8:c.1038G>C

ENST00000399240.5:c.846G>C

ENST00000437180.5:c.1119G>C

ENST00000482318.5:c.*709G>C

NM_001001890.2:c.1038G>C

NM_001754.4:c.1119G>C

NM_001001890.3:c.1038G>C

Likely Benign

BP4 BP7

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

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 variant NM_001754.5(RUNX1): c.1119G>C (p.Ser373=) is a synonymous variant. As this is a synonymous variant, there is no REVEL score however SpliceAI is ≤0.20 (0.00) (BP4). The PhyloP score is <2.0 (-0.771) (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

BP4

SpliceAI doesn't predict any significant splicing impact (SpliceAI ≤ 0.20)

BP7

SpliceAI doesn't predict any significant splicing impact (SpliceAI ≤ 0.20). The nucleotide is not highly conserved as the PhyloP score < 0.1 (Phylop score =-0.77100). No impact on splicing is predicted (SpliceAI)

PVS1

Synonymous variant therefore PVS1 is not applied

BA1

MAF of 0.00004828 (0.004828%, 2/41426 alleles) in the African/African American in gnomAD v3.1.2 cohort is < 0.0015 (0.15%) and does not meet BA1 criteria. MAF of 0.00001365 (0.001365%, 3/219806 alleles, 1 African/African American and 2 European (non-Finnish) ) in gnomAD v2.1.1 cohort is < 0.0015 (0.15%). MAF of 0.00001973 (0.001973%, 3/152082 alleles, 2 African/African American and 1 European (non-Finnish) ) in gnomAD v3.1.2 cohort is < 0.0015 (0.15%)

PM6

No case studies found

PM2

Is not completely absent from gnomad.

PM5

Synonymous variant

PM1

This variant does not affect one of the hotspot residues established by the MM-VCEP for RUNX1

PM3

This rule is not applicable for MM-VCEP

PM4

NA as is a synonymous variant

BS3

No functional studies found

BS4

No case study found

BS1

MAF of 0.00004828 (0.004828%, 2/41426 alleles) in the African/African American in gnomAD v3.1.2 cohort is < 0.00015 (0.015%) and does not meet BS1 criteria. MAF of 0.00001365 (0.001365%, 3/219806 alleles, 1 African/African American and 2 European (non-Finnish) ) in gnomAD v2.1.1 cohort is < 0.0015 (0.15%). MAF of 0.00001973 (0.001973%, 3/152082 alleles, 2 African/African American and 1 European (non-Finnish) ) in gnomAD v3.1.2 cohort is < 0.0015 (0.15%)

BS2

This rule is not applicable for MM-VCEP

BP2

No homozygotes seen in gnomAD

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

PS4

No case studies found

PS3

No functional studies found

PS2

No case studies found

PS1

Amino Acid (Ser) at 373 has not been reported as pathogenic

PP1

No case study

PP4

This rule is not applicable for MM-VCEP

PP3

SpliceAI doesn't predict any significant splicing impact

PP2

This rule is not applicable for MM-VCEP

Curation History

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