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.155T>A (p.Met52Lys)

Curation Version - 2.1
Curation History
JSON LD for Version 2.1

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: 2025-05-02

Published on: 2025-05-02

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 BP2

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

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

NM_001754.4(RUNX1):c.155T>A (p.Met52Lys) is a missense variant which has a MAF of 0.0007121 (0.071%, 840/1,179,678 alleles, including 1 homozygote) in the European (non-Finnish) subpopulation of the gnomAD v4.1.0 cohort, meeting the threshold for BS1 and BP2. 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, BP2.

BS1

MAF of 0.0007121 (0.071%, 840/1179678, 840 alleles, 1 homozygote) 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).

BP2

This variant is detected in a homozygous state in an individual or in a population database (1 homozygote) in the European (non-Finnish) subpopulation of the gnomAD v4.1.0 cohort). (BP2)

PP4

This rule is not applicable for MM-VCEP

PP1

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

PP3

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

PP2

This rule is not applicable for MM-VCEP

PM6

This variant does not have two or more assumed de novo occurrences in the literature (one occurrence confirmed as germline; for other occurrences the germline origin was not confirmed).

PM2

This variant is present in at least one population database.

PM3

This rule is not applicable for MM-VCEP

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.

PM4

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

PM5

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

BS2

This rule is not applicable for MM-VCEP

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.

BP5

This rule is not applicable for MM-VCEP

BP7

This variant is not a synonymous or intronic variant.

BP3

This rule is not applicable for MM-VCEP

BP4

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

BP1

This rule is not applicable for MM-VCEP

PVS1

This variant is not a null variant.

PS2

De novo data for this variant has not been reported in 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

PS3

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

PS1

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

BA1

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

Curation History

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