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.1196G>A (p.Ser399Asn)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410147804

964908 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9bd25f10-6539-49a3-aecb-021ccd68ce6f

Approved on: 2024-07-17

Published on: 2024-07-17

HGVS expressions

NM_001754.5:c.1196G>A

NM_001754.5(RUNX1):c.1196G>A (p.Ser399Asn)

NC_000021.9:g.34792382C>T

CM000683.2:g.34792382C>T

NC_000021.8:g.36164679C>T

CM000683.1:g.36164679C>T

NC_000021.7:g.35086549C>T

NG_011402.2:g.1197330G>A

ENST00000675419.1:c.1196G>A

ENST00000300305.7:c.1196G>A

ENST00000344691.8:c.1115G>A

ENST00000399240.5:c.923G>A

ENST00000437180.5:c.1196G>A

ENST00000482318.5:c.*786G>A

NM_001001890.2:c.1115G>A

NM_001754.4:c.1196G>A

NM_001001890.3:c.1115G>A

Uncertain Significance

PS4_Supporting BP4

PS2 PS3 PS1 PP1 PP4 PP3 PP2 PM1 PM5 PM3 PM4 PM6 PM2 PVS1 BA1 BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP3 BP1

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.1196G>A (p.Ser399Asn) is a missense variant with a REVEL score <0.50 (0.053) (BP4). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (MPN/MDS) (PMID: 32241844) (PS4_Supporting). 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: BP4, PS4_Supporting.

PS4_Supporting

This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (MPN/MDS) (PMID: 32241844) (PS4_ Supporting). This variant was reported in ClinVar in 2022 by Invitae but the affected status of the proband is unknown (Variation ID 964908).

BP4

This missense variant has a REVEL score <0.50 (0.053) (BP4).

PS2

This rule is not applicable because there is no information on affected individuals nor the family.

PS3

This rule is not met because there are no reported functional assays for this variant.

PS1

This rule is not met because the c.1196G>A variant is not a previously established pathogenic variant.

PP1

This rule is not met because there is no data available on this variant in affected members of family.

PP4

This rule is not applicable for MM-VCEP.

PP3

This rule is not met because this missense variant does not have a REVEL score >0.88.

PP2

This rule is not applicable for MM-VCEP.

PM1

This rule is not met because this variant does not affect one of the hotspot residues established by the MM-VCEP for RUNX1.

PM5

This rule is not met because other missense changes at this amino acid residue are variants of uncertain significance.

PM3

This rule is not applicable for MM-VCEP.

PM4

This rule is not met because this is a missense variant.

PM6

This rule is not applicable because there is no information on affected individuals nor the family.

PM2

This rule is not met because this missense variant has a MAF of 0.00002 (0.002%) in gnomAD v2.1.1 and v3.1.2.

PVS1

This rule is not met because this is a missense variant.

BA1

This rule is not met because this missense variant has a MAF of 0.00002 (0.002%) in gnomAD v2.1.1 and v3.1.2.

BS4

This rule is not met because there is no data available on this variant in affected members of family.

BS3

This rule is not met because there are no reported functional assays for this variant.

BS1

This rule is not met because this missense variant has a MAF not between 0.00015 (0.015%) and 0.0015 (0.15%) (0.002%) in gnomAD v2.1.1 and v3.1.2.

BS2

This rule is not applicable for MM-VCEP.

BP7

This rule is not met because this is a missense variant.

BP5

This rule is not applicable for MM-VCEP.

BP2

This rule is not applicable because there is no phase confirmation for this variant.

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

Curation History

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