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.1338C>G (p.Leu446=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA512341018

1153506 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f41a3195-9ded-462b-95ca-abf8ca25ccdc

Approved on: 2024-06-24

Published on: 2024-06-24

HGVS expressions

NM_001754.5:c.1338C>G

NM_001754.5(RUNX1):c.1338C>G (p.Leu446=)

NC_000021.9:g.34792240G>C

CM000683.2:g.34792240G>C

NC_000021.8:g.36164537G>C

CM000683.1:g.36164537G>C

NC_000021.7:g.35086407G>C

NG_011402.2:g.1197472C>G

ENST00000675419.1:c.1338C>G

ENST00000300305.7:c.1338C>G

ENST00000344691.8:c.1257C>G

ENST00000399240.5:c.1065C>G

ENST00000437180.5:c.1338C>G

ENST00000482318.5:c.*928C>G

NM_001001890.2:c.1257C>G

NM_001754.4:c.1338C>G

NM_001001890.3:c.1257C>G

Likely Benign

BP7 BP4 PM2_Supporting

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

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.1338C>G (p.Leu446=) is a synonymous variant that is not predicted to impact splicing. Since it is a synonymous variant, no REVEL score is applicable, and SpliceAI is ≤ 0.20 (0.00) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.004 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). 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: BP4, BP7, PM2_supporting.

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.004 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

BP4

Synonymous variant so no REVEL score applicable and SpliceAI is ≤0.20 (0.00) (BP4)

PM2_Supporting

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

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.

BS1

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

BP5

This rule is not applicable for MM-VCEP

BP2

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

BP3

This rule is not applicable for MM-VCEP

BP1

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

Not a missense variant

PVS1

Not a null variant

PP1

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

PP4

This rule is not applicable for MM-VCEP

PP3

No REVEL score is applicable and SpliceAI is not ≥0.38 (0.00)

PP2

This rule is not applicable for MM-VCEP

PM1

Not a missense variant

PM5

Not a missense variant

PM3

This rule is not applicable for MM-VCEP

PM4

Not a frameshift variant

PM6

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

BA1

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

Curation History

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