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.356T>C (p.Val119Ala)

CA410202782

1514344 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 68d948e8-8e9d-4000-8ea7-2a742af108cb

Approved on: 2024-07-17

Published on: 2024-07-17

HGVS expressions

NM_001754.5:c.356T>C

NM_001754.5(RUNX1):c.356T>C (p.Val119Ala)

NC_000021.9:g.34880709A>G

CM000683.2:g.34880709A>G

NC_000021.8:g.36253006A>G

CM000683.1:g.36253006A>G

NC_000021.7:g.35174876A>G

NG_011402.2:g.1109003T>C

ENST00000675419.1:c.356T>C

ENST00000300305.7:c.356T>C

ENST00000344691.8:c.275T>C

ENST00000358356.9:c.275T>C

ENST00000399237.6:c.320T>C

ENST00000399240.5:c.275T>C

ENST00000437180.5:c.356T>C

ENST00000455571.5:c.317T>C

ENST00000482318.5:c.63T>C

NM_001001890.2:c.275T>C

NM_001122607.1:c.275T>C

NM_001754.4:c.356T>C

NM_001001890.3:c.275T>C

NM_001122607.2:c.275T>C

Uncertain Significance

PM2_Supporting PP3 PM1_Supporting

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

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.356T>C (p.Val119Ala) is a missense variant that affects a residue within the Runt Homology Domain (AA 89-204) (PM1_supporting). This variant is absent from gnomAD v2.1.1 and v3.1.2 (PM2_supporting) and has a REVEL score of 0.979 (PP3). 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, PM1_supporting, PP3.

PM2_Supporting

The variant is absent from gnomAD.

PP3

The REVEL score = 0.979 which is above the threshold indicating a significant risk of pathogenicity. The SpliceAI score = 0 and therefore there is no risk that this variant impacts splicing.

PM1_Supporting

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

PS4

Not reported.

PS1

Not reported.

PS2

No published studies have included this variant.

PS3

No published studies have included this variant.

PP1

No published studies have included this variant.

PP4

This rule is not applicable for MM-VCEP

PP2

This rule is not applicable for MM-VCEP

PM6

No published studies have included this variant.

PM5

Another missense variant at this position has been called a VUS.

PM3

This rule is not applicable for MM-VCEP

PM4

This is a missense variant.

BA1

The variant is absent from gnomAD.

PVS1

This is a missense variant.

BS2

This rule is not applicable for MM-VCEP

BS4

No published studies have included this variant.

BS3

No published studies have included this variant.

BS1

The variant is absent from gnomAD.

BP2

No published studies have included this variant.

BP3

This rule is not applicable for MM-VCEP

BP4

The REVEL score = 0.979 which is above the threshold indicating a significant risk of pathogenicity. The SpliceAI score = 0 and therefore there is no risk that this variant impacts splicing.

BP1

This rule is not applicable for MM-VCEP

BP7

This variant is not an intronic or synonymous variant.

BP5

This rule is not applicable for MM-VCEP

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