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+18A>G

CA10014497

561245 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3acd6dad-0e7f-4088-849c-7852abf6a3de

HGVS expressions

NM_001754.5:c.508+18A>G

NM_001754.5(RUNX1):c.508+18A>G

NC_000021.9:g.34880539T>C

CM000683.2:g.34880539T>C

NC_000021.8:g.36252836T>C

CM000683.1:g.36252836T>C

NC_000021.7:g.35174706T>C

NG_011402.2:g.1109173A>G

ENST00000675419.1:c.508+18A>G

ENST00000300305.7:c.508+18A>G

ENST00000344691.8:c.427+18A>G

ENST00000358356.9:c.427+18A>G

ENST00000399237.6:c.472+18A>G

ENST00000399240.5:c.427+18A>G

ENST00000437180.5:c.508+18A>G

ENST00000482318.5:c.*98+18A>G

NM_001001890.2:c.427+18A>G

NM_001122607.1:c.427+18A>G

NM_001754.4:c.508+18A>G

NM_001001890.3:c.427+18A>G

NM_001122607.2:c.427+18A>G

Likely Benign

BS1 BP4 BP7

PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 PM5 PM1 PM3 PM4 PM6 PM2 PVS1 BA1 BS2 BS4 BS3 BP2 BP3 BP1 BP5

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

MAF of 0.00018 (0.018%, 23/129128 alleles) in the European (Non-Finnish) subpopulation of the gnomAD cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This intronic variant has a SpliceAI score ≤ 0.20 (0.02) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved, as it is the reference nucleotide in chimps in UCSC GRCh38 (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BP4, BP7.

BS1

MAF of 0.00018 (0.018%, 23/129128 alleles) in the European (Non-Finnish) subpopulation of the gnomAD cohort is between 0.00015 (0.015%) and 0.0015 (0.15%)

BP4

This intronic variant has a SpliceAI score ≤ 0.20 (0.02) (BP4).

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved, as it is the reference nucleotide in chimps in UCSC GRCh38.

PS4

This variant has not been reported in probands.

PS2

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

PS1

This variant does not result in an amino acid change.

PS3

This variant has not been featured in in vitro or in vivo functional studies that show damaging effect on protein function or splicing.

PP1

This variant has not been reported in affected family members.

PP4

This rule is not applicable for MM-VCEP

PP3

This variant does not have a REVEL score of ≥ 0.88 (no data returned) nor does it impactfully alter a splice site (Splice AI = 0.02).

PP2

This rule is not applicable for MM-VCEP

PM5

This variant is not a missense variant.

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

PM3

This rule is not applicable for MM-VCEP

PM4

This variant is not an indel.

PM6

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

PM2

MAF of 0.00018 (0.018%, 23/129128 alleles) in the European (Non-Finnish) subpopulation of the gnomAD cohort

PVS1

This is not a null variant.

BA1

Highest MAF is less than 0.0015 (0.15%)

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.

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

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

Approved on: 2024-06-24

Published on: 2024-06-24

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