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]

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Variant: NM_001754.5(RUNX1):c.58+23A>G

CA10014719

561249 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b9c59330-8924-465e-8c49-9cc69489ae98

Approved on: 2024-06-24

Published on: 2024-06-24

HGVS expressions

NM_001754.5:c.58+23A>G

NM_001754.5(RUNX1):c.58+23A>G

NC_000021.9:g.35048819T>C

CM000683.2:g.35048819T>C

NC_000021.8:g.36421116T>C

CM000683.1:g.36421116T>C

NC_000021.7:g.35342986T>C

NG_011402.2:g.940893A>G

ENST00000675419.1:c.58+23A>G

ENST00000300305.7:c.58+23A>G

ENST00000416754.1:c.58+23A>G

ENST00000437180.5:c.58+23A>G

ENST00000455571.5:c.58+23A>G

ENST00000475045.6:c.58+23A>G

ENST00000482318.5:c.58+23A>G

NM_001754.4:c.58+23A>G

Benign

BP2 BP4 BP7 BA1

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

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Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

This intronic variant has a MAF of 0.008015 (0.8015%, 545/67996 alleles) in the European (non-Finnish) subpopulation of gnomAD v3.1.2 cohort is ≥0.0015 (0.15%) (BA1). It is detected in a homozygous state in 9 individuals within the European (non-Finnish) population in gnomAD v2.1.1 (NB: MAF for this allele within the European (non-Finnish) population of gnomAD v2.1.1 is 0.008492 (0.8492%, 1097/129174 alleles) (BP2). It has a SpliceAI Δ score of ≤0.20 (0.00) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.666583 is <2.0). The variant is the reference nucleotide in at least 3 mammalian species. It is not the reference nucleotide in any primate (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, BP2, BP4, BP7.

BP2

This variant is detected in a homozygous state in 9 individuals within the European (non-Finnish) population in gnomAD v2.1.1 (NB: MAF for this allele within the European (non-Finnish) population in gnomAD v2.1.1 is 0.008492 (0.8492%, 1097/129174 alleles) (BP2).

BP4

This intronic variant has a SpliceAI Δ score of ≤0.20 (0.00) (BP4).

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.666583 is <2.0). The variant is the reference nucleotide in at least 3 mammalian species. It is not the reference nucleotide in any primate (BP7).

BA1

MAF of 0.008015 (0.8015%, 545/67996 alleles) in the European (non-Finnish) subpopulation of gnomAD v3.1.2 cohort is ≥0.0015 (0.15%) (BA1).

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

BP5

This rule is not applicable for MM-VCEP.

PS2

This intronic variant has not been reported in the literature.

PS4

This intronic variant has not been reported in the literature.

PS3

No functional studies reported for this variant.

PS1

This intronic variant is not predicted to impact amino acid coding.

PP1

This intronic variant has not been reported in the literature.

PP4

This rule is not applicable for MM-VCEP.

PP3

This intronic variant meets BP4 with a SpliceAI Δ score of ≤0.20 (0.00).

PP2

This rule is not applicable for MM-VCEP.

PM1

This intronic variant is not located within the RHD.

PM5

This intronic variant is not predicted to impact amino acid coding.

PM3

This rule is not applicable for MM-VCEP.

PM4

This intronic variant is not predicted to result in a protein length change.

PM6

This intronic variant has not been reported in the literature.

PM2

Meets BA1 with MAF of 0.008015 (0.8015%, 545/67996 alleles) in the European (non-Finnish) subpopulation of gnomAD v3.1.2 cohort.

PVS1

This intronic variant is not predicted to splicing or result in a null variant.

BS2

This rule is not applicable for MM-VCEP.

BS4

This intronic variant has not been reported in the literature.

BS3

No functional studies reported for this variant.

BS1

Meets BA1 with MAF of 0.008015 (0.8015%, 545/67996 alleles) in the European (non-Finnish) subpopulation of gnomAD v3.1.2 cohort.

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