ClinVar Genomic variation as it relates to human health
NM_000297.4(PKD2):c.290AGG[7] (p.Glu102dup)
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_000297.4(PKD2):c.290AGG[7] (p.Glu102dup)
Variation ID: 193079 Accession: VCV000193079.33
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 4q22.1 4: 88008021-88008022 (GRCh38) [ NCBI UCSC ] 4: 88929190-88929192 (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 Jun 28, 2015 Oct 8, 2024 Aug 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000297.4:c.290AGG[7] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000288.1:p.Glu102dup inframe insertion NM_000297.4:c.305_307dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000297.3:c.305_307dup NR_156488.2:n.389AGG[7] non-coding transcript variant NC_000004.12:g.88008023AGG[7] NC_000004.11:g.88929175AGG[7] NG_008604.1:g.5356AGG[7] - Protein change
- Other names
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- Canonical SPDI
- NC_000004.12:88008021:GAGGAGGAGGAGGAGGAGG:GAGGAGGAGGAGGAGGAGGAGG
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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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0.00739 (GAGGAGGAGGAGGAGGAGGAGG)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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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PKD2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
834 | 1067 | |
LOC129992813 | - | - | - | GRCh38 | - | 211 |
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/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 9, 2017 | RCV000173103.11 | |
Benign (1) |
criteria provided, single submitter
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Jan 26, 2024 | RCV000200241.13 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Apr 21, 2022 | RCV000987456.4 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Aug 1, 2024 | RCV001356905.16 | |
PKD2-related disorder
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Benign (1) |
no assertion criteria provided
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Oct 30, 2019 | RCV003917593.2 |
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
(Apr 26, 2017)
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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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Athena Diagnostics
Accession: SCV000614572.1
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
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Benign
(Nov 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002064908.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Likely benign
(Jul 15, 2014)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000224188.3
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
Number of individuals with the variant: 4
Sex: mixed
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Polycystic kidney disease 2
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001136751.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Oct 02, 2020)
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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: SCV001755699.1
First in ClinVar: Jul 24, 2021 Last updated: Jul 24, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 20950398, 17574468, 22863349, 21719175, 22508176)
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Likely benign
(Apr 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Polycystic kidney disease 2
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002797362.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Jan 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant polycystic kidney disease
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000255284.8
First in ClinVar: Oct 11, 2015 Last updated: Feb 14, 2024 |
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Likely benign
(Aug 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: SCV004011545.11
First in ClinVar: Jul 16, 2023 Last updated: Oct 08, 2024 |
Comment:
PKD2: BS1
Number of individuals with the variant: 2
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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: SCV001552191.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The PKD2 p.Glu102dup variant was identified in 2 of 1564 proband chromosomes (frequency: 0.001) from French, British, and North America individuals or families with ADPKD … (more)
The PKD2 p.Glu102dup variant was identified in 2 of 1564 proband chromosomes (frequency: 0.001) from French, British, and North America individuals or families with ADPKD (Audrezet 2012, Garcia-Gonzalez 2007). There is conflicting evidence in the literature and databases. The variant was identified in a 54 year old male patient with bilateral multicystic kidneys and situs inverus, the duplication segregating with the disease (cystic kidneys) in 1 of the proband’s children and was absent in the 3 unaffected children suggesting that the variant is disease causing (Bataille 2011). The variant was identified in dbSNP (ID: rs547253972) as “NA”, Clinvitae database (classification likely benign and benign), the ClinVar database (classification benign by Invitae and likely benign by Emory Genetics), the ADPKD Mutation Database (classification indeterminate), and COSMIC (1X in a lung carcinoma). This variant was also identified in the 1000 Genomes Project in 37 of 5000 chromosomes (frequency: 0.0074), HAPMAP-AFR in 32 of 1322 chromosomes (frequency: 0.0242), HAPMAP-AMR in 3 of 694 chromosomes (frequency: 0.0043), HAPMAP-EUR in 2 of 1006 chromosomes (frequency: 0.002), and in the Exome Aggregation Consortium database (August 8th 2016) in 928 of 11372 chromosomes (freq. 0.0816) in the following populations: South Asian in 662 of 7216 chromosomes (freq. 0.09), European (Non-Finnish) in 229 of 3242 chromosomes (freq. 0.07), Other in 8 of 128 chromosomes (freq. 0.06), Latino in 8 of 164 chromosomes (freq. 0.05), African in 16 of 442 chromosomes (freq. 0.04), East Asian in 5 of 172 chromosomes (freq. 0.02) but was not seen in the Finnish populations. This high frequency of observations in a control database strongly suggests that the variant is not clinically significant. 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. This variant is an in-frame duplication resulting in the addition of a Glutamic acid residue at codon 102; the impact of this alteration on PKD2 protein function is not known. 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)
Number of individuals with the variant: 2
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Benign
(Oct 30, 2019)
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no assertion criteria provided
Method: clinical testing
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PKD2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004734162.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 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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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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Clinical utility of PKD2 mutation testing in a polycystic kidney disease cohort attending a specialist nephrology out-patient clinic. | Robinson C | BMC nephrology | 2012 | PMID: 22863349 |
Association of PKD2 (polycystin 2) mutations with left-right laterality defects. | Bataille S | American journal of kidney diseases : the official journal of the National Kidney Foundation | 2011 | PMID: 21719175 |
Aberrant PKD2 splicing due to a presumed novel missense mutation in autosomal-dominant polycystic kidney disease. | Tan YC | Clinical genetics | 2011 | PMID: 20950398 |
Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. | Garcia-Gonzalez MA | Molecular genetics and metabolism | 2007 | PMID: 17574468 |
Text-mined citations for rs750077647 ...
HelpRecord last updated Oct 13, 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.