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+1G>A

CA410203336

561236 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 603cd528-c485-4e30-934a-cabde6c6d80d

HGVS expressions

NM_001754.5:c.351+1G>A

NM_001754.5(RUNX1):c.351+1G>A

NC_000021.9:g.34886842C>T

CM000683.2:g.34886842C>T

NC_000021.8:g.36259139C>T

CM000683.1:g.36259139C>T

NC_000021.7:g.35181009C>T

NG_011402.2:g.1102870G>A

ENST00000675419.1:c.351+1G>A

ENST00000300305.7:c.351+1G>A

ENST00000344691.8:c.270+1G>A

ENST00000358356.9:c.270+1G>A

ENST00000399237.6:c.315+1G>A

ENST00000399240.5:c.270+1G>A

ENST00000437180.5:c.351+1G>A

ENST00000455571.5:c.312+1G>A

ENST00000482318.5:c.59-6129G>A

NM_001001890.2:c.270+1G>A

NM_001122607.1:c.270+1G>A

NM_001754.4:c.351+1G>A

NM_001001890.3:c.270+1G>A

NM_001122607.2:c.270+1G>A

Pathogenic

PVS1 PM5_Supporting PM2_Supporting PS4_Moderate

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

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The c.351+1G>A is a splice donor variant that is predicted to introduce exon 4 skipping and a frameshift with a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). This variant has been reported in two probands meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 27931139). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PS4_Supporting, PM5_supporting.

PVS1

The c.351+1G>A is a splice donor variant that is predicted to introduce exon 4 skipping and a frameshift with a premature stop codon and expected to result in nonsense-mediated mRNA decay.

PM5_Supporting

This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting).

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

PS4_Moderate

2 probands (1 from PMID: 27931139 and 1 unpublished) meet RUNX1 phenotype criteria.

PM3

MM-VCEP deemed N/A for RUNX1

PM1

This variant is not a missense variant.

PM4

This variant is not an in-frame deletion/insertion.

PM6

No data currently available

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

BS3

No data currently available

BS4

No evidence

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

BS2

MM-VCEP deemed N/A for RUNX1

BP5

MM-VCEP deemed N/A for RUNX1

BP7

This variant is not a synonymous or intronic variant.

BP2

No evidence

BP3

MM-VCEP deemed N/A for RUNX1

BP4

This variant does not have applicable in-silico data available.

BP1

MM-VCEP deemed N/A for RUNX1

PS2

No data currently available

PS3

No data currently available

PS1

This variant is not a missense, or synonymous variant.

PP4

MM-VCEP deemed N/A for RUNX1

PP3

This variant does not have applicable in-silico data available.

PP2

MM-VCEP deemed N/A for RUNX1

PP1

Not enough segregations (at least 3) reported in families in the literature to apply PP1.

Approved on: 2024-03-26

Published on: 2024-03-26

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