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.998C>T (p.Pro333Leu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014224

1015734 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 219b425e-9af3-407d-832d-11b828a030a3

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.998C>T

NM_001754.5(RUNX1):c.998C>T (p.Pro333Leu)

NC_000021.9:g.34792580G>A

CM000683.2:g.34792580G>A

NC_000021.8:g.36164877G>A

CM000683.1:g.36164877G>A

NC_000021.7:g.35086747G>A

NG_011402.2:g.1197132C>T

ENST00000675419.1:c.998C>T

ENST00000300305.7:c.998C>T

ENST00000344691.8:c.917C>T

ENST00000399240.5:c.725C>T

ENST00000437180.5:c.998C>T

ENST00000482318.5:c.*588C>T

NM_001001890.2:c.917C>T

NM_001754.4:c.998C>T

NM_001001890.3:c.917C>T

Likely Benign

BS1 BP4

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

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Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.998C>T (p.Pro333Leu) is a missense variant with a MAF of 0.0001937 (0.01937%, 1/5162, 1 allele) in the East Asian subpopulation of the gnomAD v3.1.2 cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This missense variant has a REVEL score < 0.50 (0.346) and a SpliceAI score ≤ 0.20 (0.0) (BP4). 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, BP4.

BS1

MAF of 0.0001937 (0.01937%, 1/5162, 1 allele) in the East Asian subpopulation of the gnomAD v3.1.2 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1).

BP4

This missense variant has a REVEL score < 0.50 (0.346) and a SpliceAI score ≤ 0.20 (0.0) (BP4).

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.

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.

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for MM-VCEP.

PS2

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

PS4

Proband 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.

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.

PP1

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

PP4

This rule is not applicable for MM-VCEP.

PP3

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

PP2

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.

PM5

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

PM3

This rule is not applicable for MM-VCEP.

PM4

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

PM6

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

PM2

This variant is present in at least one population database.

PVS1

This variant is not a null variant.

Curation History

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