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]

Variant: NM_001754.5(RUNX1):c.1268G>C (p.Arg423Pro)

CA410147569

579565 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: 6ca7de45-ad81-4ca4-9f9e-8b128ed07c9f

Approved on: 2025-02-24

Published on: 2025-02-24

HGVS expressions

NM_001754.5(RUNX1):c.1268G>C (p.Arg423Pro)

NM_001754.5:c.1268G>C

NC_000021.9:g.34792310C>G

CM000683.2:g.34792310C>G

NC_000021.8:g.36164607C>G

CM000683.1:g.36164607C>G

NC_000021.7:g.35086477C>G

NG_011402.2:g.1197402G>C

ENST00000675419.1:c.1268G>C

ENST00000300305.7:c.1268G>C

ENST00000344691.8:c.1187G>C

ENST00000399240.5:c.995G>C

ENST00000437180.5:c.1268G>C

ENST00000482318.5:c.*858G>C

NM_001001890.2:c.1187G>C

NM_001754.4:c.1268G>C

NM_001001890.3:c.1187G>C

Likely Benign

BS1 BP4

BS2 BS3 BS4 BP1 BP2 BP3 BP7 BP5 PS2 PS3 PS4 PVS1 PP2 PP1 PP4 PM6 PM1 PM3 PM4

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.1268G>C (p.Arg423Pro) is a missense variant. MAF of 0.0001793 (0.01793%, 5/27882 alleles) in the Ashkenazi Jewish subpopulation of the gnomAD v4.1.0 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This missense variant has a REVEL score < 0.50 (0.486) and a SpliceAI score ≤ 0.20 (0.0) (BP4). 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.

BS1

gnomAD v.4.1.0: 5/27882 alleles in Ashkenazi Jewish, MAF: 0.01793%; 1/5850 alleles in Middle Eastern, MAF 0.017%. Total 102 alleles/1531096, MAF 0.006662%. MAF of 0.0001793 (0.01793%, 5/27882 alleles) in the Ashkenazi Jewish subpopulation of the gnomAD v4.1.0 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1).

BP4

-REVEL: 0.486 - SplicAI: 0 This missense variant has a REVEL score < 0.50 (0.486) and a SpliceAI score ≤ 0.20 (0) (BP4).

BS2

This rule is not applicable for MM-VCEP

BS3

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

BS4

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

BP1

This rule is not applicable for MM-VCEP

BP2

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

BP3

This rule is not applicable for MM-VCEP

BP7

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

BP5

This rule is not applicable for MM-VCEP

PS2

De novo data for this variant has not been reported in literature.

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS4

The germline variant has not been reported, but the variant has been detected in a gastric cancer at a VAF<5% (PMID: 30239046).

PVS1

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

PP2

This rule is not applicable for MM-VCEP

PP1

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

PP4

This rule is not applicable for MM-VCEP

PM6

De novo data for this variant has not been reported in literature.

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 OR within residues 89-204.

PM3

This rule is not applicable for MM-VCEP

PM4

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

Curation History

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