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.502G>T (p.Gly168Ter)

CA410202477

627081 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ecb6ba2c-4c06-46c6-b200-df0a4983562f

HGVS expressions

NM_001754.5:c.502G>T

NM_001754.5(RUNX1):c.502G>T (p.Gly168Ter)

NC_000021.9:g.34880563C>A

CM000683.2:g.34880563C>A

NC_000021.8:g.36252860C>A

CM000683.1:g.36252860C>A

NC_000021.7:g.35174730C>A

NG_011402.2:g.1109149G>T

ENST00000675419.1:c.502G>T

ENST00000300305.7:c.502G>T

ENST00000344691.8:c.421G>T

ENST00000358356.9:c.421G>T

ENST00000399237.6:c.466G>T

ENST00000399240.5:c.421G>T

ENST00000437180.5:c.502G>T

ENST00000482318.5:c.*92G>T

NM_001001890.2:c.421G>T

NM_001122607.1:c.421G>T

NM_001754.4:c.502G>T

NM_001001890.3:c.421G>T

NM_001122607.2:c.421G>T

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PVS1 PM2_Supporting

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

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

This variant NM_001754.5(RUNX1):c.502G>T (p.Gly168Ter) is a nonsense variant predicted to undergo NMD (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1 and PM2_supporting.

PVS1

Gly168Ter is a nonsense variant predicted to undergo NMD

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1

PS4

No case studies found

PS2

No case studies found

PS1

Amino acid (Gly) at position 168 has not been established as pathogenic

PS3

No functional studies found

PM5

MM-VCEP has found c.502G>A as a VUS and does not qualify for PM5

PM1

This variant affects one of the other residues (AA 89-204) within the RHD however not a missense variant

PM3

This rule is not applicable for MM-VCEP

PM4

Termination of sequence not applied by PM4

PM6

No case studies found

BA1

Meets PM2

BP2

No homozygotes found in gnomAD

BP3

This rule is not applicable for MM-VCEP

BP4

Not a missense variant therefore no REVEL score and SpliceAI is not ≥0.38 (0.01 donor loss)

BP1

This rule is not applicable for MM-VCEP

BP7

Not a synonymous or intronic variant

BP5

This rule is not applicable for MM-VCEP

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BS1

Meets PM2

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Not a missense variant therefore no REVEL score and SpliceAI is not ≥0.38 (0.01 donor loss)

PP2

This rule is not applicable for MM-VCEP

Approved on: 2022-01-20

Published on: 2022-07-08

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