ClinVar Genomic variation as it relates to human health
NM_001754.5(RUNX1):c.167T>C (p.Leu56Ser)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001754.5(RUNX1):c.167T>C (p.Leu56Ser)
Variation ID: 239045 Accession: VCV000239045.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q22.12 21: 34887027 (GRCh38) [ NCBI UCSC ] 21: 36259324 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 2, 2016 Apr 15, 2024 Jul 26, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001754.5:c.167T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001745.2:p.Leu56Ser missense NM_001001890.3:c.86T>C NP_001001890.1:p.Leu29Ser missense NM_001122607.2:c.86T>C NP_001116079.1:p.Leu29Ser missense NC_000021.9:g.34887027A>G NC_000021.8:g.36259324A>G NG_011402.2:g.1102685T>C LRG_482:g.1102685T>C LRG_482t1:c.167T>C LRG_482p1:p.Leu56Ser - Protein change
- L56S, L29S
- Other names
- NM_001754.4(RUNX1):c.167T>C
- Canonical SPDI
- NC_000021.9:34887026:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.01038 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.01038
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01059
Trans-Omics for Precision Medicine (TOPMed) 0.01216
Exome Aggregation Consortium (ExAC) 0.01629
1000 Genomes Project 30x 0.01015
The Genome Aggregation Database (gnomAD) 0.01206
The Genome Aggregation Database (gnomAD), exomes 0.01519
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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RUNX1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1236 | 1577 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (6) |
reviewed by expert panel
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Jul 26, 2019 | RCV000226755.20 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2023 | RCV000680395.12 | |
Benign (1) |
criteria provided, single submitter
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Oct 21, 2020 | RCV002256141.2 | |
Benign (2) |
criteria provided, single submitter
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Jul 7, 2023 | RCV002277588.3 | |
Benign (1) |
criteria provided, single submitter
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Oct 22, 2019 | RCV003891806.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Jul 26, 2019)
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reviewed by expert panel
Method: curation
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Familial platelet disorder with associated myeloid malignancy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Myeloid Malignancy Variant Curation Expert Panel
Accession: SCV000965641.1
First in ClinVar: Aug 18, 2019 Last updated: Aug 18, 2019 |
Comment:
The NM_001754.4:c.167T>C (p.Leu56Ser) variant has a MAF of 0.03259 (3.259%, 518/15,894 alleles) in the South Asian subpopulation of the ExAC cohort that is >/= 0.0015 … (more)
The NM_001754.4:c.167T>C (p.Leu56Ser) variant has a MAF of 0.03259 (3.259%, 518/15,894 alleles) in the South Asian subpopulation of the ExAC cohort that is >/= 0.0015 (0.15%) (BA1). This variant is detected in homozygous state (56) in gnomAD population database (BP2). Transactivation assays demonstrating normal transactivation (80-115% of wt) and data from secondary assays demonstrate normal DNA binding, CBF-beta binding and sub-cellular localization (BS3; PMID: 23817177). Two patients reported in PMID:29365323 with AML. But PS4 can not apply in combined with BA1. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BS3, BP2. (less)
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Benign
(Jan 08, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743126.1 First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000435952.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Jul 12, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001753940.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 31385734, 31289210, 11921279, 21343560, 27106701, 22753902, 28386644)
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Benign
(Oct 21, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002535853.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Acute myeloid leukemia
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015357.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000287182.8
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
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Benign
(Oct 22, 2019)
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criteria provided, single submitter
Method: clinical testing
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RUNX1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000308031.3
First in ClinVar: Oct 02, 2016 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Benign
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV003916330.7
First in ClinVar: Apr 23, 2023 Last updated: Apr 15, 2024 |
Comment:
RUNX1: PP3, BS1, BS2
Number of individuals with the variant: 6
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Benign
(May 08, 2015)
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no assertion criteria provided
Method: clinical testing
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Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745582.1 First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798345.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: research
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Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Affected status: yes
Allele origin:
unknown
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ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology
Accession: SCV002515757.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Acute Myeloid Leukemia
Affected status: yes
Allele origin:
somatic
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Nadeem Sheikh Lab, University of the Punjab
Accession: SCV002564649.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
Ethnicity/Population group: South Asian
Geographic origin: Pakistan
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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RUNX1 meets MLL: epigenetic regulation of hematopoiesis by two leukemia genes. | Koh CP | Leukemia | 2013 | PMID: 23817177 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/36a19c90-310a-4c8f-ad1d-8f186170daaa | - | - | - | - |
Text-mined citations for rs111527738 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.