Evidence Repository - GenboreeKB

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_001754.4(RUNX1):c.976G>T (p.Asp326Tyr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410148817

581331 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ea02a531-8c2f-48cd-9a21-68ec84cb451a

Approved on: 2020-02-12

Published on: 2020-06-02

HGVS expressions

NM_001754.4:c.976G>T

NM_001754.4(RUNX1):c.976G>T (p.Asp326Tyr)

NC_000021.9:g.34792602C>A

CM000683.2:g.34792602C>A

NC_000021.8:g.36164899C>A

CM000683.1:g.36164899C>A

NC_000021.7:g.35086769C>A

NG_011402.2:g.1197110G>T

ENST00000675419.1:c.976G>T

ENST00000300305.7:c.976G>T

ENST00000344691.8:c.895G>T

ENST00000399240.5:c.703G>T

ENST00000437180.5:c.976G>T

ENST00000482318.5:c.*566G>T

NM_001001890.2:c.895G>T

NM_001001890.3:c.895G>T

NM_001754.5:c.976G>T

Uncertain Significance

PM2

PM6 PM1 PM3 PM5 PM4 BA1 PVS1 BS2 BS1 BS4 BS3 BP4 BP3 BP1 BP2 BP5 BP7 PS1 PS2 PS3 PS4 PP1 PP2 PP3 PP4

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The NM_001754.4:c.976G>T variant results in the Asp326Tyr change. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). This variant has not been reported in the literature, to the best of our knowledge. 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: PM2.

PM2

The variant is absent from gnomAD and meets PM2

PM6

No data currently available

PM1

N/A

PM3

MM-VCEP deemed N/A for RUNX1

PM5

Asp326Asn is a variant at the same residue and has not been evaluated by the MM-VCEP.

PM4

N/A

BA1

Variant meets PM2

PVS1

N/A

BS2

MM-VCEP deemed N/A for RUNX1

BS1

Variant meets PM2

BS4

No data currently available

BS3

No data currently available

BP4

REVEL score > 0.15

BP3

MM-VCEP deemed N/A for RUNX1

BP1

MM-VCEP deemed N/A for RUNX1

BP2

No data currently available

BP5

MM-VCEP deemed N/A for RUNX1

BP7

N/A

PS1

No data currently available

PS2

No data currently available

PS3

No data currently available

PS4

From internal laboratory data (SCV000834105.1): Patient does not meet RUNX1 phenotype criteria.

PP1

No data currently available

PP2

MM-VCEP deemed N/A for RUNX1

PP3

The variant has a REVEL score of 0.275 which does not meet the criteria for PP3 (threshold >0.75).

PP4

MM-VCEP deemed N/A for RUNX1

Curation History

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