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.
ClinVar Genomic variation as it relates to human health
NM_002691.4(POLD1):c.1665C>T (p.Val555=)
Germline
Classification
Help
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.
(14)
Help
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.
Benign/Likely benign
14
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_002691.4(POLD1):c.1665C>T (p.Val555=)
Variation ID: 239248 Accession: VCV000239248.62
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.33 19: 50407153 (GRCh38) [ NCBI UCSC ] 19: 50910410 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 28, 2017 Oct 20, 2024 Aug 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_002691.4:c.1665C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002682.2:p.Val555= synonymous NM_001256849.1:c.1665C>T NP_001243778.1:p.Val555= synonymous NM_001308632.1:c.1665C>T NP_001295561.1:p.Val555= synonymous NR_046402.2:n.1710C>T non-coding transcript variant NC_000019.10:g.50407153C>T NC_000019.9:g.50910410C>T NG_033800.1:g.27831C>T LRG_785:g.27831C>T LRG_785t1:c.1665C>T LRG_785p1:p.Val555= LRG_785t2:c.1665C>T LRG_785p2:p.Val555= - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000019.10:50407152:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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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0.00020 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
The Genome Aggregation Database (gnomAD) 0.00053
Trans-Omics for Precision Medicine (TOPMed) 0.00054
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00069
The Genome Aggregation Database (gnomAD), exomes 0.00078
Exome Aggregation Consortium (ExAC) 0.00092
- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| POLD1 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4946 | 4996 | |
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. |
|---|---|---|---|---|
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000439741.22 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 1, 2020 | RCV000574633.5 | |
| Benign (1) |
criteria provided, single submitter
|
Feb 1, 2024 | RCV001082021.10 | |
| Likely benign (1) |
no assertion criteria provided
|
- | RCV001354171.4 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000759940.35 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Dec 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000520753.4
First in ClinVar: Mar 08, 2017 Last updated: Apr 09, 2018 |
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)
|
|
|
Benign
(Jan 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806472.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Benign
(Apr 30, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159617.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
|
|
|
Benign
(Oct 26, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000889655.3
First in ClinVar: Mar 14, 2019 Last updated: Jan 01, 2022 |
|
|
|
Likely benign
(Jan 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002065991.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Benign
(Oct 01, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002534600.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
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Likely benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551921.4
First in ClinVar: Jul 27, 2022 Last updated: Aug 18, 2023 |
|
|
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Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Colorectal cancer, susceptibility to, 10
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000287529.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
|
|
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Likely benign
(Jun 18, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000670902.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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)
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005205898.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
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Likely benign
(Aug 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001152029.27
First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024 |
Comment:
POLD1: BP4, BP7, BS1
Number of individuals with the variant: 8
|
|
|
Likely benign
(Apr 06, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000805285.1
First in ClinVar: Jan 01, 2018 Last updated: Jan 01, 2018 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001548715.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The POLD1 p.Val555= variant was not identified in the literature. The variant was identified in dbSNP (rs150238541) as “with likely benign allele” and ClinVar (classified … (more)
The POLD1 p.Val555= variant was not identified in the literature. The variant was identified in dbSNP (rs150238541) as “with likely benign allele” and ClinVar (classified as likely benign by Ambry Genetics, GeneDx, True Health Diagnostics and 2 other submitters; and as benign by Invitae and Prevention Genetics). The variant was identified in control databases in 206 of 279,020 chromosomes (2 homozygous) at a frequency of 0.0007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 43 of 30,490 chromosomes (freq: 0.001), European in 142 of 126,522 chromosomes (freq: 0.001), Other in 4 of 7138 chromosomes (freq: 0.0006), Finnish in 13 of 24,740 chromosomes (freq: 0.0005), Ashkenazi Jewish in 1 of 10,192 chromosomes (freq: 0.0001), African in 2 of 24,900 chromosomes (freq: 0.00008), and Latino in 1 of 35,130 chromosomes (freq: 0.00003), while it was not observed in the East Asian population. The p.Val555= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001973940.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Comment:
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Comment:
POLD1: BP4, BP7, BS1
Comment:
The POLD1 p.Val555= variant was not identified in the literature. The variant was identified in dbSNP (rs150238541) as “with likely benign allele” and ClinVar (classified as likely benign by Ambry Genetics, GeneDx, True Health Diagnostics and 2 other submitters; and as benign by Invitae and Prevention Genetics). The variant was identified in control databases in 206 of 279,020 chromosomes (2 homozygous) at a frequency of 0.0007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 43 of 30,490 chromosomes (freq: 0.001), European in 142 of 126,522 chromosomes (freq: 0.001), Other in 4 of 7138 chromosomes (freq: 0.0006), Finnish in 13 of 24,740 chromosomes (freq: 0.0005), Ashkenazi Jewish in 1 of 10,192 chromosomes (freq: 0.0001), African in 2 of 24,900 chromosomes (freq: 0.00008), and Latino in 1 of 35,130 chromosomes (freq: 0.00003), while it was not observed in the East Asian population. The p.Val555= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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.
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. |
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 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.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Comment:
POLD1: BP4, BP7, BS1
Comment:
The POLD1 p.Val555= variant was not identified in the literature. The variant was identified in dbSNP (rs150238541) as “with likely benign allele” and ClinVar (classified as likely benign by Ambry Genetics, GeneDx, True Health Diagnostics and 2 other submitters; and as benign by Invitae and Prevention Genetics). The variant was identified in control databases in 206 of 279,020 chromosomes (2 homozygous) at a frequency of 0.0007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 43 of 30,490 chromosomes (freq: 0.001), European in 142 of 126,522 chromosomes (freq: 0.001), Other in 4 of 7138 chromosomes (freq: 0.0006), Finnish in 13 of 24,740 chromosomes (freq: 0.0005), Ashkenazi Jewish in 1 of 10,192 chromosomes (freq: 0.0001), African in 2 of 24,900 chromosomes (freq: 0.00008), and Latino in 1 of 35,130 chromosomes (freq: 0.00003), while it was not observed in the East Asian population. The p.Val555= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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.
Citations for germline classification of this variant
Help| There 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 rs150238541 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 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.