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.351+5T>C

CA658656804

463992 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9b5b124c-a288-45ac-993a-2f5a43354f85

Approved on: 2022-08-23

Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.351+5T>C

NM_001754.5(RUNX1):c.351+5T>C

NC_000021.9:g.34886838A>G

CM000683.2:g.34886838A>G

NC_000021.8:g.36259135A>G

CM000683.1:g.36259135A>G

NC_000021.7:g.35181005A>G

NG_011402.2:g.1102874T>C

ENST00000675419.1:c.351+5T>C

ENST00000300305.7:c.351+5T>C

ENST00000344691.8:c.270+5T>C

ENST00000358356.9:c.270+5T>C

ENST00000399237.6:c.315+5T>C

ENST00000399240.5:c.270+5T>C

ENST00000437180.5:c.351+5T>C

ENST00000455571.5:c.312+5T>C

ENST00000482318.5:c.59-6125T>C

NM_001001890.2:c.270+5T>C

NM_001122607.1:c.270+5T>C

NM_001754.4:c.351+5T>C

NM_001001890.3:c.270+5T>C

NM_001122607.2:c.270+5T>C

Likely Benign

PM2_Supporting BP7 BP4

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

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.351+5T>C is an intronic variant has spliceAI ∆ scores ≤ 0.20 (BP4)Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score (0.3) < 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: PM2_supporting, BP4, BP7.

PM2_Supporting

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

BP7

BP7: Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score (0.3) < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

BP4

BP4: This intronic variant has spliceAI ∆ scores ≤ 0.20

PS2

nil data

PS4

nil data

PS3

nil data

PS1

intronic variant

PVS1

intronic variant not involving canonical splice site

PP4

not applicable

PP1

nil data

PP3

intronic variant

PP2

not applicable

PM6

nil data

PM1

Variant IS NOT affecting one of the following amino acid residues within RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204

PM4

intronic variant

PM5

intronic variant

BA1

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

BS4

nil data

BS3

nil data

BS1

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

BS2

not applicable

BP3

intronic variant

BP1

not applicable

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