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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001754.5(RUNX1):c.361C>G (p.Leu121Val)

CA410202773

2088789 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 916b85ea-801f-4895-bf04-401e7ed5982b

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.361C>G

NM_001754.5(RUNX1):c.361C>G (p.Leu121Val)

NC_000021.9:g.34880704G>C

CM000683.2:g.34880704G>C

NC_000021.8:g.36253001G>C

CM000683.1:g.36253001G>C

NC_000021.7:g.35174871G>C

NG_011402.2:g.1109008C>G

ENST00000675419.1:c.361C>G

ENST00000300305.7:c.361C>G

ENST00000344691.8:c.280C>G

ENST00000358356.9:c.280C>G

ENST00000399237.6:c.325C>G

ENST00000399240.5:c.280C>G

ENST00000437180.5:c.361C>G

ENST00000455571.5:c.322C>G

ENST00000482318.5:c.68C>G

NM_001001890.2:c.280C>G

NM_001122607.1:c.280C>G

NM_001754.4:c.361C>G

NM_001001890.3:c.280C>G

NM_001122607.2:c.280C>G

Uncertain Significance

PM1_Supporting PM2_Supporting PP3

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

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.361C>G (p.Leu121Val) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This missense variant has a REVEL score ≥ 0.88 (0.883) (PP3). This missense variant is located within the Runt Homology Domain (AA 89-204), but does not occur in an established hotspot residue (PM1_supporting). This variant was also reported in ClinVar in 2022 by Invitae but the affected status of the proband is unknown (Variation ID 2088789). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PP3, PM1_supporting, PM2_supporting.

PM1_Supporting

This missense variant affects one of the other residues (AA 89-204) within the RHD (PM1_supporting).

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting).

PP3

This missense variant has a REVEL score ≥ 0.88 (0.883) (PP3).

BA1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2

PM5

This variant is a missense change at the same residue (p.L121V) where one different missense changes have been previously established as variant of uncertain significance (ClinVar ID 1363734).

PM3

Rule is not applicable according to MM-VCEP.

PM4

This variant is missense.

PM6

This variant has not been reported in the literature.

BS2

Rule is not applicable according to MM-VCEP.

BS4

This variant has not been reported in the literature.

BS3

This variant has no functional evidence reported in the literature.

BS1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2.

BP2

This variant has not been reported in the literature.

BP3

Rule is not applicable according to MM-VCEP.

BP4

This missense variant has a REVEL score ≥ 0.50 (0.883).

BP1

Rule is not applicable according to MM-VCEP.

PVS1

This variant is missense.

BP7

This variant is missense.

BP5

Rule is not applicable according to MM-VCEP.

PS2

This variant has not been reported in the literature.

PS4

This variant has not been reported in the literature. This variant was reported in ClinVar in 2022 by Invitae but the affected status of the proband is unknown (Variation ID 2088789).

PS3

This variant has no functional evidence reported in the literature.

PS1

This variant is not the same amino acid change as previously established pathogenic variants curated using MM-VCEP rules for RUNX1.

PP1

This variant has not been reported in the literature.

PP4

Rule is not applicable according to MM-VCEP.

PP2

Rule is not applicable according to MM-VCEP.

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