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.1020C>G (p.Pro340=)

CA512341366

758049 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: 95d282c7-2a56-469b-b26c-ecde2f514069

Approved on: 2022-01-20

Published on: 2022-06-30

HGVS expressions

NM_001754.5:c.1020C>G

NM_001754.5(RUNX1):c.1020C>G (p.Pro340=)

NC_000021.9:g.34792558G>C

CM000683.2:g.34792558G>C

NC_000021.8:g.36164855G>C

CM000683.1:g.36164855G>C

NC_000021.7:g.35086725G>C

NG_011402.2:g.1197154C>G

ENST00000675419.1:c.1020C>G

ENST00000300305.7:c.1020C>G

ENST00000344691.8:c.939C>G

ENST00000399240.5:c.747C>G

ENST00000437180.5:c.1020C>G

ENST00000482318.5:c.*610C>G

NM_001001890.2:c.939C>G

NM_001754.4:c.1020C>G

NM_001001890.3:c.939C>G

Likely Benign

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

BP4 BP7 PM2_Supporting

PM5 PM1 PM3 PM4 PM6 BS2 BS4 BS3 BS1 PVS1 PS4 PS2 PS1 PS3 BP2 BP3 BP1 BP5 BA1 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.1020C>G (p.Pro340=) is a synonymous variant. As it is a synonymous variant there is no REVEL score but SpliceAI is ≤0.20 (0.00) (BP4). The PhyloP Score is <2.0 (-0.628) (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, PM2_supporting.

BP4

Synonymous variant, therefore, has no REVEL score but SpliceAI is ≤0.20 (0.00)

BP7

PhyloP Score is <2.0 (-0.628)

PM2_Supporting

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

PM5

Synonymous variant does not meet PM5

PM1

Synonymous variant outside of hotspot/ critical domain

PM3

This rule is not applicable for MM-VCEP

PM4

Synonymous variant does not meet PM4

PM6

No case studies found

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No functional studies found

BS1

Meets PM2.

PVS1

Synonymous variant does not meet PVS1

PS4

No case studies found

PS2

No case studies found

PS1

Amino acid (proline) at 340 change has not been recorded as pathogenic.

PS3

No functional studies found

BP2

No homozygotes reported in gnomAD

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

BA1

Meets PM2.

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Synonymous variant, therefore, does not have a REVEl score and SpliceAI is not ≥0.38 (0.00)

PP2

This rule is not applicable for MM-VCEP

Curation History

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