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.1197C>G (p.Ser399Arg)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410147801

2150091 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9eee86f8-307c-4e57-8b85-47655fdec3b3

Approved on: 2024-07-17

Published on: 2024-07-17

HGVS expressions

NM_001754.5:c.1197C>G

NM_001754.5(RUNX1):c.1197C>G (p.Ser399Arg)

NC_000021.9:g.34792381G>C

CM000683.2:g.34792381G>C

NC_000021.8:g.36164678G>C

CM000683.1:g.36164678G>C

NC_000021.7:g.35086548G>C

NG_011402.2:g.1197331C>G

ENST00000675419.1:c.1197C>G

ENST00000300305.7:c.1197C>G

ENST00000344691.8:c.1116C>G

ENST00000399240.5:c.924C>G

ENST00000437180.5:c.1197C>G

ENST00000482318.5:c.*787C>G

NM_001001890.2:c.1116C>G

NM_001754.4:c.1197C>G

NM_001001890.3:c.1116C>G

Uncertain Significance

BP4 PM2_Supporting

PS1 PS2 PS4 PS3 PP1 PP4 PP3 PP2 PM6 PM5 PM1 PM3 PM4 PVS1 BS2 BS4 BS3 BS1 BP7 BP5 BP2 BP3 BP1 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.1197C>G (p.Ser399Arg) is a missense mutation that is not present in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This variant has a REVEL score < 0.50 (0.126), and a SpliceAI score ≤ 0.20 (0.0) (BP4). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria have been applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4.

BP4

REVEL score = 0.126 which is below threshold for pathogenicity and SpliceAI score = 0.

PM2_Supporting

Variant is not present in gnomAD.

PS1

Not found.

PS2

Variant has not been reported in the literature.

PS4

Variant has not been reported in the literature.

PS3

Variant has not been reported in the literature.

PP1

Variant has not been reported in the literature.

PP4

This rule is not applicable for MM-VCEP

PP3

REVEL score = 0.126 which is below threshold for pathogenicity and SpliceAI score = 0.

PP2

This rule is not applicable for MM-VCEP

PM6

Variant has not been reported in the literature.

PM5

Other missense changes at this codon are also VUS.

PM1

This residue is not within the RUNX1 hotspot region.

PM3

This rule is not applicable for MM-VCEP

PM4

Variant is a missense mutation.

PVS1

Variant is a missense mutation.

BS2

This rule is not applicable for MM-VCEP

BS4

Variant has not been reported in the literature.

BS3

Variant has not been reported in the literature.

BS1

Variant is not present in gnomAD.

BP7

Variant is a missense mutation.

BP5

This rule is not applicable for MM-VCEP

BP2

Variant has not been reported in the literature.

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BA1

Variant is not present in gnomAD.

Curation History

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