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.508+10C>G

CA2499225877

1150822 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e717bfb3-2a8e-4eea-a347-6017a096ae3d

HGVS expressions

NM_001754.5:c.508+10C>G

NM_001754.5(RUNX1):c.508+10C>G

NC_000021.9:g.34880547G>C

CM000683.2:g.34880547G>C

NC_000021.8:g.36252844G>C

CM000683.1:g.36252844G>C

NC_000021.7:g.35174714G>C

NG_011402.2:g.1109165C>G

ENST00000675419.1:c.508+10C>G

ENST00000300305.7:c.508+10C>G

ENST00000344691.8:c.427+10C>G

ENST00000358356.9:c.427+10C>G

ENST00000399237.6:c.472+10C>G

ENST00000399240.5:c.427+10C>G

ENST00000437180.5:c.508+10C>G

ENST00000482318.5:c.*98+10C>G

NM_001001890.2:c.427+10C>G

NM_001122607.1:c.427+10C>G

NM_001754.4:c.508+10C>G

NM_001001890.3:c.427+10C>G

NM_001122607.2:c.427+10C>G

Uncertain Significance

BP4 PM2_Supporting

PS2 PS4 PS3 PS1 BP7 BP5 BP3 BP2 BP1 PP1 PP4 PP3 PP2 BA1 PM1 PM4 PM5 PM3 PVS1 PM6 BS2 BS4 BS3 BS1

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

NM_001754.5(RUNX1):c.508+10C>G is an intronic variant. In summary, the clinical significance of this variant is uncertain. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). REVEL score not applicable and SpliceAI is ≤0.20 (0.02) (BP4). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM2_supporting

BP4

This synonymous/intronic variant does not has a SpliceAI score of ≤ 0.20 (Donor Gain 0.02)

PM2_Supporting

Variant is not present in population databases (gnomAD v2.1 or v3.1.2)

PS2

This variant has not been found to co-segregate with the disease in the literature.

PS4

This variant has not been reported in probands.

PS3

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PS1

This is not a missense variant, and there has not yet been a missense change determined to be pathogenic at this amino acid residue.

BP7

Evolutionary conservation prediction algorithms predict the site as being conserved (PhyloP score 5.87 > 2.0).

BP5

This rule is not applicable for MM-VCEP

BP3

This rule is not applicable for MM-VCEP

BP2

This variant has not been found to co-segregate with the disease in the literature.

BP1

This rule is not applicable for MM-VCEP

PP1

This variant was not found to co-segregate with disease in multiple affected family members.

PP4

This rule is not applicable for MM-VCEP

PP3

This synonymous/intronic variant does not have a SpliceAI score of ≥ 0.38 (Donor Gain 0.02)

PP2

This rule is not applicable for MM-VCEP

BA1

Variant is not present in population databases (gnomAD v2.1 or v3.1.2)

PM1

This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 NOR is it within residues 89-204

PM4

This variant is not an indel.

PM5

This is not a missense variant, and there has not yet been a different missense change determined to be pathogenic at this amino acid residue.

PM3

This rule is not applicable for MM-VCEP

PVS1

This variant is not a null variant.

PM6

This variant has not been reported in probands in the literature.

BS2

This rule is not applicable for MM-VCEP

BS4

This variant has not been reported in affected family members.

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

BS1

Variant is not present in population databases (gnomAD v2.1 or v3.1.2)

Approved on: 2022-08-23

Published on: 2023-11-13

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