ClinVar Genomic variation as it relates to human health
NM_002691.4(POLD1):c.88C>T (p.Arg30Trp)
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_002691.4(POLD1):c.88C>T (p.Arg30Trp)
Variation ID: 221163 Accession: VCV000221163.48
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.33 19: 50398939 (GRCh38) [ NCBI UCSC ] 19: 50902196 (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 Feb 2, 2016 Apr 15, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002691.4:c.88C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002682.2:p.Arg30Trp missense NM_001256849.1:c.88C>T NP_001243778.1:p.Arg30Trp missense NM_001308632.1:c.88C>T NP_001295561.1:p.Arg30Trp missense NR_046402.2:n.133C>T non-coding transcript variant NC_000019.10:g.50398939C>T NC_000019.9:g.50902196C>T NG_033800.1:g.19617C>T LRG_785:g.19617C>T LRG_785t1:c.88C>T LRG_785p1:p.Arg30Trp LRG_785t2:c.88C>T LRG_785p2:p.Arg30Trp P28340:p.Arg30Trp - Protein change
- R30W
- Other names
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- Canonical SPDI
- NC_000019.10:50398938: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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0.00379 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00344
The Genome Aggregation Database (gnomAD) 0.00706
Trans-Omics for Precision Medicine (TOPMed) 0.00713
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00962
The Genome Aggregation Database (gnomAD), exomes 0.00821
Exome Aggregation Consortium (ExAC) 0.01267
1000 Genomes Project 0.00379
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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POLD1 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4815 | 4864 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000204228.20 | |
Benign (7) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000420692.27 | |
Benign (2) |
criteria provided, single submitter
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May 20, 2015 | RCV000576004.10 | |
Benign (5) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000588327.30 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 16, 2022 | RCV002500664.8 |
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
(Aug 25, 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: SCV000698017.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The c.88C>T (p.Arg30Trp) in POLD1 gene is a missense change that involves a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. … (more)
Variant summary: The c.88C>T (p.Arg30Trp) in POLD1 gene is a missense change that involves a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. The variant is present in the control population dataset of ExAC at an overall frequency 0.013 (671/52972 chrs tested) including 5 homozygotes. This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0000142). The variant was identified in a clinical case, which also carried a known pathogenic mutation, c.68_69delAG, in BRCA1 gene. The variant is cited as Benign by a reputable database/clinical laboratory. Taking together, the variant was classified as Benign. (less)
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Benign
(Nov 17, 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: SCV000517983.4
First in ClinVar: Mar 08, 2017 Last updated: Sep 28, 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
(Dec 09, 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: SCV000806568.1
First in ClinVar: Sep 28, 2017 Last updated: Sep 28, 2017 |
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Benign
(May 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000670882.4
First in ClinVar: Jan 01, 2018 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Benign
(Jun 10, 2016)
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criteria provided, single submitter
Method: clinical testing
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Colorectal cancer, susceptibility to, 10
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000488499.2
First in ClinVar: Feb 02, 2016 Last updated: Dec 24, 2022 |
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Benign
(Jul 05, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000889699.3
First in ClinVar: Mar 13, 2019 Last updated: Dec 31, 2022 |
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Likely benign
(Mar 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Colorectal cancer, susceptibility to, 10
Mandibular hypoplasia-deafness-progeroid syndrome
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002807079.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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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, 10
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016621.1
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: SCV002552079.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Colorectal cancer, susceptibility to, 10
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000262391.8
First in ClinVar: Feb 02, 2016 Last updated: Feb 14, 2024 |
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Benign
(Sep 28, 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: SCV001157561.6
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Mar 01, 2024)
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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: SCV002563542.10
First in ClinVar: Aug 23, 2022 Last updated: Apr 15, 2024 |
Comment:
POLD1: BP4, BS1, BS2
Number of individuals with the variant: 61
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Likely benign
(Dec 01, 2017)
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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: SCV000788155.1
First in ClinVar: Jan 01, 2018 Last updated: Jan 01, 2018 |
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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:
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: SCV001552549.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The POLD1 p.Arg30Trp variant was identified in 1 of 58 proband chromosomes (frequency: 0.02) from individuals or families with HNPCC (Talseth-Palmer 2015). The variant was … (more)
The POLD1 p.Arg30Trp variant was identified in 1 of 58 proband chromosomes (frequency: 0.02) from individuals or families with HNPCC (Talseth-Palmer 2015). The variant was also identified in dbSNP (ID: rs3218772) as "With Benign allele", ClinVar (classified as benign by Invitae, Counsyl, GeneDx, Ambry Genetics and three other clinical laboratories), Cosmic (1x in prostate tissue), and MutDB. The variant was identified in control databases in 1935 of 241054 chromosomes (13 homozygous) at a frequency of 0.008, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 1228 of 108476 chromosomes (freq: 0.01), South Asian in 299 of 26820 chromosomes (freq: 0.01), African in 28 of 21060 chromosomes (freq: 0.001), Other in 62 of 5816 chromosomes (freq: 0.01), Latino in 183 of 30048 chromosomes (freq: 0.006), Ashkenazi Jewish in 74 of 9266 chromosomes (freq: 0.0079), and Finnish in 61 of 22694 chromosomes (freq: 0.0026), while the variant was not observed in the East Asian population. The p.Arg30 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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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: SCV001800303.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 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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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809052.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 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: SCV001925200.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 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 Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001977649.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 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
HelpTitle | Author | Journal | Year | Link |
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Targeted next-generation sequencing of 22 mismatch repair genes identifies Lynch syndrome families. | Talseth-Palmer BA | Cancer medicine | 2016 | PMID: 26811195 |
Text-mined citations for rs3218772 ...
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.