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.294C>G (p.Leu98=)

CA512318850

532678 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ad7b74a0-29c0-4a48-81da-c451f9edf8cb

HGVS expressions

NM_001754.5:c.294C>G

NM_001754.5(RUNX1):c.294C>G (p.Leu98=)

NC_000021.9:g.34886900G>C

CM000683.2:g.34886900G>C

NC_000021.8:g.36259197G>C

CM000683.1:g.36259197G>C

NC_000021.7:g.35181067G>C

NG_011402.2:g.1102812C>G

ENST00000675419.1:c.294C>G

ENST00000300305.7:c.294C>G

ENST00000344691.8:c.213C>G

ENST00000358356.9:c.213C>G

ENST00000399237.6:c.258C>G

ENST00000399240.5:c.213C>G

ENST00000437180.5:c.294C>G

ENST00000455571.5:c.255C>G

ENST00000482318.5:c.59-6187C>G

NM_001001890.2:c.213C>G

NM_001122607.1:c.213C>G

NM_001754.4:c.294C>G

NM_001001890.3:c.213C>G

NM_001122607.2:c.213C>G

Likely Benign

BP4 BP7 PM2_Supporting

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

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The c.294C>G (p.Leu98=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing (BP4); in addition, an evolutionary conservation algorithm predicts the site as being not highly conserved (PhyloP score = 1.16043 in GRCh38) (BP7). Although the variant is absent from from gnomAD v2 and v3 (PM2_Supporting), it also has not been reported in cases or the literature. In summary, this variant meets the criteria to be classified as likely benign for hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: BP4, BP7, and PM2_Supporting.

BP4

SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).

BP7

The variant is not predicted by SpliceAI to impact splicing. In addition, an evolutionary conservation algorithm predicts the site as being weakly conserved (PhyloP score = 1.16043 in GRCh38).

PM2_Supporting

Completely absent from gnomAD with a mean coverage of at least 20X (v2 and v3).

PVS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS2

Not applicable

BS3

No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

BS4

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

BS1

Completely absent from gnomAD with a mean coverage of at least 20X (v2 and v3).

BP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP3

Not applicable

BP1

Not applicable

BP5

Not applicable

PS2

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PS4

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PS3

No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PS1

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

BA1

Completely absent from gnomAD with a mean coverage of at least 20X (v2 and v3).

PP1

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PP4

Not applicable

PP3

SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).

PP2

Not applicable

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM3

Not applicable

PM4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM6

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

Approved on: 2023-11-13

Published on: 2023-11-13

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