ClinVar Genomic variation as it relates to human health
NM_006231.4(POLE):c.2174-8G>A
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_006231.4(POLE):c.2174-8G>A
Variation ID: 220785 Accession: VCV000220785.39
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q24.33 12: 132667656 (GRCh38) [ NCBI UCSC ] 12: 133244242 (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 Mar 8, 2017 Feb 20, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006231.4:c.2174-8G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000012.12:g.132667656C>T NC_000012.11:g.133244242C>T NG_033840.1:g.24869G>A LRG_789:g.24869G>A LRG_789t1:c.2174-8G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000012.12:132667655:C:T
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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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0.00459 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00422
1000 Genomes Project 0.00459
Trans-Omics for Precision Medicine (TOPMed) 0.00996
The Genome Aggregation Database (gnomAD) 0.01137
The Genome Aggregation Database (gnomAD), exomes 0.01188
Exome Aggregation Consortium (ExAC) 0.01205
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01330
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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POLE | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9003 | 9213 |
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 (1) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV000204595.18 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000424665.30 | |
Likely benign (1) |
no assertion criteria provided
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Feb 14, 2018 | RCV000664288.9 | |
Benign (5) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000586345.22 | |
Benign (1) |
no assertion criteria provided
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- | RCV001355620.9 |
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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Likely benign
(Mar 29, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000540087.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 1.7% European, intronic (less)
Method: Genome/Exome Filtration
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Benign
(Nov 18, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000518044.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000261617.8
First in ClinVar: Feb 02, 2016 Last updated: Feb 14, 2024 |
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Benign
(Aug 17, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698663.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: c.2174-8G>A in POLE gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not … (more)
Variant summary: c.2174-8G>A in POLE gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.012 (1461/121260 chrs tested), including 4 homozygous occurrences. The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.000014, suggesting that it is a benign polymorphism. The variant of interest has been reported as Benign/Polymorphism by reputable database/clinical laboratory. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. (less)
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Benign
(Nov 22, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000806741.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Colorectal cancer, susceptibility to, 12
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004017075.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550156.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
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Benign
(Feb 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888511.4
First in ClinVar: Mar 17, 2018 Last updated: Jan 06, 2024 |
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Benign
(Feb 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157477.6
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Likely benign
(Feb 14, 2018)
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no assertion criteria provided
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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True Health Diagnostics
Accession: SCV000788166.1
First in ClinVar: Jul 28, 2018 Last updated: Jul 28, 2018 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550554.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The POLE c.2174-8G>A variant was not identified in the literature nor was it identified in the Cosmic and MutDB databases. The variant was identified in … (more)
The POLE c.2174-8G>A variant was not identified in the literature nor was it identified in the Cosmic and MutDB databases. The variant was identified in dbSNP (ID: rs117409343) as “With other allele”, ClinVar and Clinvitae (5x as benign by Invitae, GeneDx, Quest diagnostics, Laboratory Corporation of America and likely benign by Laboratory for molecular Medicine). The variant was identified in control databases in 3277 of 276912 chromosomes (25 homozygous) at a frequency of 0.012 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 75 of 24034 chromosomes (freq: 0.003), Other in 88 of 6458 chromosomes (freq: 0.013), Latino in 291 of 34418 chromosomes (freq: 0.008), European Non-Finnish in 2146 of 126616 chromosomes (freq: 0.017), Ashkenazi Jewish in 87 of 10152 chromosomes (freq: 0.008), East Asian in 1 of 18870 chromosomes (freq: 0.000053), European Finnish in 502 of 25584 chromosomes (freq: 0.02), and South Asian in 87 of 30780 chromosomes (freq: 0.003). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808532.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917672.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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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)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002036643.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs117409343 ...
HelpRecord last updated May 12, 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.