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+259C>T

CA14885658

1222743 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: db91b5d3-0a90-4abc-a719-0f04ac66a2fe

Approved on: 2024-08-28

Published on: 2024-08-28

HGVS expressions

NM_001754.5:c.508+259C>T

NM_001754.5(RUNX1):c.508+259C>T

NC_000021.9:g.34880298G>A

CM000683.2:g.34880298G>A

NC_000021.8:g.36252595G>A

CM000683.1:g.36252595G>A

NC_000021.7:g.35174465G>A

NG_011402.2:g.1109414C>T

ENST00000675419.1:c.508+259C>T

ENST00000300305.7:c.508+259C>T

ENST00000344691.8:c.427+259C>T

ENST00000358356.9:c.427+259C>T

ENST00000399237.6:c.472+259C>T

ENST00000399240.5:c.427+259C>T

ENST00000437180.5:c.508+259C>T

ENST00000482318.5:c.*98+259C>T

NM_001001890.2:c.427+259C>T

NM_001122607.1:c.427+259C>T

NM_001754.4:c.508+259C>T

NM_001001890.3:c.427+259C>T

NM_001122607.2:c.427+259C>T

Benign

BA1 BP7 BP2 BP4

PVS1 BP5 BP3 BP1 BS4 BS3 BS1 BS2 PP1 PP4 PP3 PP2 PS2 PS4 PS3 PS1 PM1 PM5 PM3 PM4 PM6 PM2

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

NM_001754.5(RUNX1):c.508+259C>T is an intronic variant with a MAF of 0.2807 (28.07%, 2440/8694,) in the African/African American subpopulation of gnomAD cohort is ≥ 0.0015 (0.15%) (BA1). This variant is observed in 942 homozygotes in a population database (gnomAD) (BP2). This intronic variant has a SpliceAI score ≤ 0.20 (Acceptor Loss 0.0) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.65 < 2.0) (BP7). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4, BP7, BP2

BA1

MAF of 0.2807 (28.07%, 2440/8694,) in the African/African American subpopulation of gnomAD cohort is ≥ 0.0015 (0.15%).

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.65 < 2.0)

BP2

This variant is observed in 942 homozygotes in a population database (gnomAD).

BP4

This synonymous/intronic/UTR/frameshift variant has a SpliceAI score ≤ 0.20 (Acceptor Loss 0.0).

PVS1

This variant is not a null variant, as it does not impact any of the following processes or sites: Nonsense, frameshift, canonical +/- 1 or 2 splice sites, initiation codon, single exon deletion, multiple exon deletions

BP5

This rule is not applicable for the MM-VCEP

BP3

This rule is not applicable for the MM-VCEP

BP1

This rule is not applicable for the 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 showing no damaging effect on the gene or gene product.

BS1

BS1 cannot be applied with BA1.

BS2

This rule is not applicable for the MM-VCEP

PP1

This variant has not been reported in affected family members.

PP4

This rule is not applicable for the MM-VCEP

PP3

This synonymous/intronic variant does not have a SpliceAI score of ≥ 0.38 (Acceptor Loss 0.00).

PP2

This rule is not applicable for the MM-VCEP

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 an amino acid change determined to be pathogenic at this amino acid residue.

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

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 the MM-VCEP

PM4

This variant is not an inframe indel.

PM6

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

PM2

This variant is present in population databases with at least 20x coverage for RUNX1.

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