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>T (p.Lys215Asn)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410207064

936839 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ed990cfc-bb59-4859-8564-b8c9a4339560

Approved on: 2024-10-29

Published on: 2024-10-29

HGVS expressions

NM_001754.5:c.645G>T

NM_001754.5(RUNX1):c.645G>T (p.Lys215Asn)

NC_000021.9:g.34834570C>A

CM000683.2:g.34834570C>A

NC_000021.8:g.36206867C>A

CM000683.1:g.36206867C>A

NC_000021.7:g.35128737C>A

NG_011402.2:g.1155142G>T

ENST00000675419.1:c.645G>T

ENST00000300305.7:c.645G>T

ENST00000344691.8:c.564G>T

ENST00000358356.9:c.564G>T

ENST00000399237.6:c.609G>T

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

ENST00000437180.5:c.645G>T

ENST00000469087.1:n.181G>T

ENST00000482318.5:c.*235G>T

NM_001001890.2:c.564G>T

NM_001122607.1:c.564G>T

NM_001754.4:c.645G>T

NM_001001890.3:c.564G>T

NM_001122607.2:c.564G>T

Uncertain Significance

PM2_Supporting

BS2 BS4 BS3 BS1 BP7 BP5 BP2 BP3 BP4 BP1 PM5 PM1 PM3 PM4 PM6 PS4 PS1 PS2 PS3 PP1 PP4 PP3 PP2 BA1 PVS1

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>T (p.Lys215Asn) is a missense variant which is absent from both gnomAD v2.1 and gnomAD v3.1.2 (PM2_supporting). This variant has not been reported in any proband meeting at least one of the RUNX1-phenotypic criteria. In summary, this variant meets the criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

BS2

This rule is not applicable for MM-VCEP

BS4

No case study found

BS3

No studies found

BS1

PM2_Supporting met

BP7

This is a missense variant with no predicted splice effect

BP5

This rule is not applicable for MM-VCEP

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP4

REVEL score is >0.50 (REVEL score=0.721)

BP1

This rule is not applicable for MM-VCEP

PM5

Amino acid 215 has not been previously observed as pathogenic

PM1

This variant effects amino acid 215 which is outside of the RUNT domain

PM3

This rule is not applicable for MM-VCEP

PM4

This is a missense variant

PM6

No case study found

PS4

No proband meeting RUNX1 FPD-MM phenotypic criteria has been described

PS1

Amino acid 215 has not been previously observed as pathogenic

PS2

No case study found

PS3

No studies found

PP1

No case study found

PP4

This rule is not applicable for MM-VCEP

PP3

REVEL score is <0.88 (REVEL score=0.721)

PP2

This rule is not applicable for MM-VCEP

BA1

PM2_Supporting met

PVS1

This is not a loss of function variant

Curation History

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