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.108G>A (p.Thr36=)

CA512318998

1153275 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c94626c8-7bdf-4e67-8010-2cd126c6812a

Approved on: 2022-04-08

Published on: 2022-07-05

HGVS expressions

NM_001754.5:c.108G>A

NM_001754.5(RUNX1):c.108G>A (p.Thr36=)

NC_000021.9:g.34887086C>T

CM000683.2:g.34887086C>T

NC_000021.8:g.36259383C>T

CM000683.1:g.36259383C>T

NC_000021.7:g.35181253C>T

NG_011402.2:g.1102626G>A

ENST00000675419.1:c.108G>A

ENST00000300305.7:c.108G>A

ENST00000344691.8:c.27G>A

ENST00000358356.9:c.27G>A

ENST00000399237.6:c.72G>A

ENST00000399240.5:c.27G>A

ENST00000437180.5:c.108G>A

ENST00000455571.5:c.69G>A

ENST00000475045.6:c.108G>A

ENST00000482318.5:c.59-6373G>A

NM_001001890.2:c.27G>A

NM_001122607.1:c.27G>A

NM_001754.4:c.108G>A

NM_001001890.3:c.27G>A

NM_001122607.2:c.27G>A

Likely Benign

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

BP7 BP4 PM2_Supporting

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

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.108G>A (p.Thr36=) is a synonymous variant therefore REVEL score is not applicable and SpliceAI is ≤0.20 (acceptor loss 0.01) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.43361 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). 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 benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, and PM2_supporting

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.43361 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

BP4

Synonymous variant therefore REVEL score is not applicable and SpliceAI is ≤0.20 (acceptor loss 0.01) (BP4)

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

BA1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BP5

This rule is not applicable for MM-VCEP

BP3

This rule is not applicable for MM-VCEP

BP2

No homozygotes present on gnomAD v2.1.1 and v3.1.2

BP1

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BS1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BS2

This rule is not applicable for MM-VCEP

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Synonymous variant therefore REVEL score is not applicable and SpliceAI is NOT ≥0.38 (acceptor loss 0.01)

PP2

This rule is not applicable for MM-VCEP

PS4

No case studies found

PS2

No case studies found

PS3

No functional studies found

PS1

The amino acid location has not been previously established as pathogenic

PM1

Not a missense variant

PM5

Not a missense variant

PM4

Not an inframe deletion/insertion

PM3

This rule is not applicable for MM-VCEP

PM6

No case studies found

PVS1

Not a null variant

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