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.645G>A (p.Lys215=)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA512318690

464001 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 0db785bf-1e86-4ff3-b502-5b777605f7f2

Approved on: 2025-02-24

Published on: 2025-02-24

HGVS expressions

NM_001754.5:c.645G>A

NM_001754.5(RUNX1):c.645G>A (p.Lys215=)

NC_000021.9:g.34834570C>T

CM000683.2:g.34834570C>T

NC_000021.8:g.36206867C>T

CM000683.1:g.36206867C>T

NC_000021.7:g.35128737C>T

NG_011402.2:g.1155142G>A

ENST00000675419.1:c.645G>A

ENST00000300305.7:c.645G>A

ENST00000344691.8:c.564G>A

ENST00000358356.9:c.564G>A

ENST00000399237.6:c.609G>A

ENST00000399240.5:c.532+24904G>A

ENST00000437180.5:c.645G>A

ENST00000469087.1:n.181G>A

ENST00000482318.5:c.*235G>A

NM_001001890.2:c.564G>A

NM_001122607.1:c.564G>A

NM_001754.4:c.645G>A

NM_001001890.3:c.564G>A

NM_001122607.2:c.564G>A

Uncertain Significance

BP4

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

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

NM_001754.5(RUNX1):c.645G>A (p.Lys215=) is a synonymous variant not predicted to affect splicing (BP4). However, evolutionary conservation prediction algorithms predict the site as being moderately conserved (PhyloP score: 5.81) and the variant is not the reference nucleotide in one primate and/or three mammal species. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4.

BP4

Splice AI=0

BP2

No case study found

BP3

Not applicable

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BP7

Evolutionary conservation prediction algorithms predict the site as being moderately conserved (PhyloP score: 5.81 ) and the variant is not the reference nucleotide in one primate and/or three mammal species.

PS4

No proband meeting RUNX1 FPDMM phenotypic criteria described

PS2

No case study found

PS3

No functional studies found

PS1

No pathogenic variant has been identified at amino acid 215

PP1

no case study found

PP4

This rule is not applicable for MM-VCEP

PP3

BP4 met

PP2

This rule is not applicable for MM-VCEP

PM6

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

ALL:0.0012% (3/250556 alleles) - EAS:0.0054% - OTH:0.033% (gnomAD v2) Not present in gnomAD v3

PM3

Not applicable

PM5

No pathogenic variant has been identified at amino acid 215

PM1

Not at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 89-204.

PM4

No change in protein length

BA1

ALL:0.0012% (3/250556 alleles) - EAS:0.0054% - OTH:0.033% (gnomAD v2) Not present in gnomAD v3

BS2

This rule is not applicable for MM-VCEP

PVS1

This is not a null variant

BS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

No functional studies found

BS1

ALL:0.0012% (3/250556 alleles) - EAS:0.0054% - OTH:0.033% (gnomAD v2) Not present in gnomAD v3

Curation History

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