Evidence Repository - GenboreeKB

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.155T>A (p.Met52Lys)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA10014581

239044 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4ceacdfa-56c1-4933-a48a-f8c97e4f92e9

Approved on: 2025-04-01

Published on: 2025-04-01

HGVS expressions

NM_001754.5:c.155T>A

NM_001754.5(RUNX1):c.155T>A (p.Met52Lys)

NC_000021.9:g.34887039A>T

CM000683.2:g.34887039A>T

NC_000021.8:g.36259336A>T

CM000683.1:g.36259336A>T

NC_000021.7:g.35181206A>T

NG_011402.2:g.1102673T>A

ENST00000675419.1:c.155T>A

ENST00000300305.7:c.155T>A

ENST00000344691.8:c.74T>A

ENST00000358356.9:c.74T>A

ENST00000399237.6:c.119T>A

ENST00000399240.5:c.74T>A

ENST00000437180.5:c.155T>A

ENST00000455571.5:c.116T>A

ENST00000482318.5:c.59-6326T>A

NM_001001890.2:c.74T>A

NM_001122607.1:c.74T>A

NM_001754.4:c.155T>A

NM_001001890.3:c.74T>A

NM_001122607.2:c.74T>A

Likely Benign

BS1

BS4 BS3 BS2 BP5 BP7 BP4 BP3 BP1 BP2 PVS1 PM6 PM2 PM1 PM3 PM5 PM4 PS1 PS2 PS3 PS4 BA1 PP1 PP2 PP3 PP4

Evidence Links 1

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 NM_001754.4:c.155T>A (p.Met52Lys) is a missense variant. This variant has a MAF of 0.0007121 (0.071%, 840/1179678, 840 alleles) in the European (non-Finnish) subpopulation of the gnomAD v4.1.0 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). 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: BS1.

BS1

MAF of 0.0007121 (0.071%, 840/1179678, 840 alleles) in the European (non-Finnish) subpopulation of the gnomAD v4.1.0 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1).

BS4

Segregation data for this variant has not been reported in literature.

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS2

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BP7

This variant is not a synonymous or intronic variant.

BP4

This missense variant does not have a REVEL score < 0.50.

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

PVS1

This variant is not a null variant.

PM6

De novo data for this variant has not been reported in literature

PM2

This variant is present in at least one population database.

PM1

This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.

PM3

This rule is not applicable for MM-VCEP

PM5

There has not yet been a different missense change determined to be pathogenic at this amino acid residue.

PM4

This variant is not an in-frame deletion/insertion.

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

PS2

De novo data for this variant has not been reported in literature

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS4

PS4 cannot be applied because the variant presents more than 2 times in gnomAD

Pt 9 with AML, germline variant on cultured skin fibroblasts PubMed:29365323

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

PP1

Segregation data for this variant has not been reported in literature.

PP2

This rule is not applicable for MM-VCEP

PP3

This missense variant does not have a REVEL score of ≥ 0.88.

PP4

This rule is not applicable for MM-VCEP

Curation History

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