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.1396A>G (p.Met466Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014177

1002421 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 32058939-e3a4-4a3d-8d5c-78f1fe956233

Approved on: 2023-11-13

Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.1396A>G

NM_001754.5(RUNX1):c.1396A>G (p.Met466Val)

NC_000021.9:g.34792182T>C

CM000683.2:g.34792182T>C

NC_000021.8:g.36164479T>C

CM000683.1:g.36164479T>C

NC_000021.7:g.35086349T>C

NG_011402.2:g.1197530A>G

ENST00000675419.1:c.1396A>G

ENST00000300305.7:c.1396A>G

ENST00000344691.8:c.1315A>G

ENST00000399240.5:c.1123A>G

ENST00000437180.5:c.1396A>G

ENST00000482318.5:c.*986A>G

NM_001001890.2:c.1315A>G

NM_001754.4:c.1396A>G

NM_001001890.3:c.1315A>G

Uncertain Significance

BP4

BS2 BS4 BS3 BS1 BP3 BP2 BP1 BP5 BP7 BA1 PS3 PS2 PS1 PS4 PP4 PP1 PP3 PP2 PVS1 PM4 PM1 PM3 PM5 PM6 PM2

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.1396A>G (p.Met466Val) is a missense variant that has a REVEL score ≤0.50 (0.203) and SpliceAI is ≤0.20 (0.00) (BP4). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4.

BP4

This variant has a REVEL score ≤0.50 (0.203) and SpliceAI is ≤0.20 (0.00) (BP4)

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BS1

Variant only present in gnomAD v2.1.1 and does not meet code criteria

BP3

This rule is not applicable for MM-VCEP

BP2

Variant only present in gnomAD v2.1.1 and does not meet code criteria

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BP7

Not a synonymous or intronic variant

BA1

Variant only present in gnomAD v2.1.1 and does not meet code criteria

PS3

No functional studies found

PS2

No case studies found

PS1

Amino Acid location has been curated as Benign by MMVCEP

PS4

This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 32855275) however not confirmed as germline

PP4

This rule is not applicable for MM-VCEP

PP1

No case studies found

PP3

This variant has a REVEL score ≤0.50 (0.203) and SpliceAI is ≤0.20 (0.00)

PP2

This rule is not applicable for MM-VCEP

PVS1

Not a null/truncating variant

PM4

Not an in-frame deletion/insertion

PM1

Not located in a hotspot or a critical region

PM3

This rule is not applicable for MM-VCEP

PM5

Amino Acid location has been curated as Benign by MMVCEP

PM6

No case studies found

PM2

Variant only present in gnomAD v2.1.1 and does not meet code criteria

Curation History

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