ClinVar Genomic variation as it relates to human health
NM_000297.4(PKD2):c.916C>T (p.Arg306Ter)
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
-
NM_000297.4(PKD2):c.916C>T (p.Arg306Ter)
Variation ID: 397507 Accession: VCV000397507.18
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4q22.1 4: 88038323 (GRCh38) [ NCBI UCSC ] 4: 88959475 (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 Mar 27, 2017 Feb 14, 2024 Feb 7, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000297.4:c.916C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000288.1:p.Arg306Ter nonsense NR_156488.2:n.1015C>T non-coding transcript variant NC_000004.12:g.88038323C>T NC_000004.11:g.88959475C>T NG_008604.1:g.35656C>T - Protein change
- R306*
- Other names
- -
- Canonical SPDI
- NC_000004.12:88038322: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.
-
0.00020 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
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. |
|||
PKD2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
775 | 997 |
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. |
---|---|---|---|---|
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jun 17, 2021 | RCV000449565.7 | |
Pathogenic (1) |
no assertion criteria provided
|
- | RCV001292151.2 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Feb 7, 2023 | RCV000681703.7 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 11, 2021 | RCV001861649.4 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Jul 12, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Polycystic kidney disease 2
Affected status: yes
Allele origin:
germline
|
Center of Genomic medicine, Geneva, University Hospital of Geneva
Accession: SCV000537693.1
First in ClinVar: Mar 27, 2017 Last updated: Mar 27, 2017 |
Age: 0-5 years
Sex: female
|
|
Pathogenic
(Sep 16, 2018)
|
criteria provided, single submitter
Method: research
|
not provided
Affected status: yes
Allele origin:
germline
|
Gharavi Laboratory, Columbia University
Accession: SCV000809155.1
First in ClinVar: Oct 01, 2018 Last updated: Oct 01, 2018 |
|
|
Pathogenic
(Feb 01, 2020)
|
criteria provided, single submitter
Method: research
|
Polycystic kidney disease 2
Affected status: yes
Allele origin:
paternal
|
Molecular Biology Laboratory, Fundació Puigvert
Study: KidneyPanel_2020
Accession: SCV001425219.1 First in ClinVar: Jan 17, 2021 Last updated: Jan 17, 2021 |
|
|
Pathogenic
(Jan 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research
Accession: SCV001422338.1
First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020 |
|
|
Pathogenic
(Jan 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Polycystic kidney disease 2
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001368854.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PP3.
|
|
Pathogenic
(Jun 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Polycystic kidney disease 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen
Accession: SCV001750073.1
First in ClinVar: Jul 15, 2021 Last updated: Jul 15, 2021 |
Comment:
The change is listed in the dbSNP database (dbSNP151, as of June 17, 2021) with the rs number rs200001068. In gnomAD it is reported with … (more)
The change is listed in the dbSNP database (dbSNP151, as of June 17, 2021) with the rs number rs200001068. In gnomAD it is reported with a frequency of 0.0003981% (1/251172) (as of June 17, 2021). The variant is mentioned as pathogenic both in ClinVar (including RCV000449565.3) and in the renowned PKD mutation database (http://pkd.mayo.edu; as of June 17, 2021). The variant has been described several times in the literature in patients with ADPKD (including Audrézet et al., 2012). In the case of stop or nonsense variants in a gene that matches the phenotype, there is also a high probability of pathogenic relevance. At this point in time, the variant is to be regarded as a "pathogenic variant" (ACMG criteria). (less)
Sex: male
|
|
Pathogenic
(Jun 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics Inc
Accession: SCV002771629.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with … (more)
This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. (less)
|
|
Pathogenic
(Dec 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002520136.2
First in ClinVar: May 28, 2022 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 24113780, 31589614, 33532864, 29633482, 31740684, 9326320, 29529603, 33437033, 16430766, 14993477, 23300259, 32970388, 18837007, 11968093, 24374109, 10760080) (less)
|
|
Pathogenic
(Feb 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226766.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP1, PM2_supporting, PS4_moderate, PVS1
Number of individuals with the variant: 1
|
|
Pathogenic
(Oct 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant polycystic kidney disease
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002240561.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 397507). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 397507). This premature translational stop signal has been observed in individual(s) with polycystic kidney disease (PMID: 9326320, 29529603). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg306*) in the PKD2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKD2 are known to be pathogenic (PMID: 17582161, 22863349). (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Polycystic Kidney disease
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: SCV001480728.1 First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Comment:
The PKD2 p.Arg306* variant was identified in 13 of 3960 proband chromosomes (frequency: 0.003) from individuals or families with autosomal dominant polycystic kidney disease (ADPKD; … (more)
The PKD2 p.Arg306* variant was identified in 13 of 3960 proband chromosomes (frequency: 0.003) from individuals or families with autosomal dominant polycystic kidney disease (ADPKD; Audrezet 2012, Garcia-Gonzalez 2007, Magistroni 2003, Reiterova 2002, Rossetti 2007, Rossetti 2012, Stekrova 2004, Tan 2008, Torra 2000, Veldhuisen 1997, Vouk 2006). The variant was also identified in ClinVar (classified as pathogenic by Center of Genomic Medicine Geneva and Gharavi Laboratory at Columbia University), LOVD 3.0 (3x), and ADPKD Mutation Database (as definitely pathogenic). The variant was not identified in dbSNP or PKD1-LOVD. The variant was identified in control databases in 1 of 245930 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 1 of 111434 chromosomes (freq: 0.000009); it was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The c.916C>T variant leads to a premature stop codon at position 306, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the PKD2 gene are an established mechanism of disease in ADPKD and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
Number of individuals with the variant: 1
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players. | Domingo-Gallego A | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2022 | PMID: 33532864 |
PKD2 gene variants in Chinese patients with autosomal dominant polycystic kidney disease. | Xu D | Clinical genetics | 2021 | PMID: 34101167 |
Genomic diagnostics in polycystic kidney disease: an assessment of real-world use of whole-genome sequencing. | Mallawaarachchi AC | European journal of human genetics : EJHG | 2021 | PMID: 33437033 |
Disease causing property analyzation of variants in 12 Chinese families with polycystic kidney disease. | Dong K | Molecular genetics & genomic medicine | 2020 | PMID: 32970388 |
Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing. | Kim H | Scientific reports | 2019 | PMID: 31740684 |
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. | Capalbo A | PLoS genetics | 2019 | PMID: 31589614 |
Diagnostic Utility of Exome Sequencing for Kidney Disease. | Groopman EE | The New England journal of medicine | 2019 | PMID: 30586318 |
Identification of novel mutations and risk assessment of Han Chinese patients with autosomal dominant polycystic kidney disease. | Zhang M | Nephrology (Carlton, Vic.) | 2019 | PMID: 29633482 |
Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease. | Xu D | Kidney & blood pressure research | 2018 | PMID: 29529603 |
Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). | Carrera P | Scientific reports | 2016 | PMID: 27499327 |
Arterial aneurysms: autosomal dominant polycystic kidney disease, Marfan syndrome or both? | Riccio E | Clinical and experimental nephrology | 2014 | PMID: 24113780 |
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 |
Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. | Audrézet MP | Human mutation | 2012 | PMID: 22508176 |
Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease. | Tan YC | Human mutation | 2009 | PMID: 18837007 |
Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. | Rossetti S | Journal of the American Society of Nephrology : JASN | 2007 | PMID: 17582161 |
Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. | Garcia-Gonzalez MA | Molecular genetics and metabolism | 2007 | PMID: 17574468 |
PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease. | Vouk K | BMC medical genetics | 2006 | PMID: 16430766 |
PKD2 mutations in a Czech population with autosomal dominant polycystic kidney disease. | Stekrová J | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2004 | PMID: 14993477 |
Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. | Magistroni R | Journal of the American Society of Nephrology : JASN | 2003 | PMID: 12707387 |
Four novel mutations of the PKD2 gene in Czech families with autosomal dominant polycystic kidney disease. | Reiterová J | Human mutation | 2002 | PMID: 11968093 |
Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients. | Torra R | American journal of kidney diseases : the official journal of the National Kidney Foundation | 2000 | PMID: 11007674 |
Location of mutations within the PKD2 gene influences clinical outcome. | Hateboer N | Kidney international | 2000 | PMID: 10760080 |
A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2). | Veldhuisen B | American journal of human genetics | 1997 | PMID: 9326320 |
click to load more click to collapse |
Text-mined citations for rs200001068 ...
HelpRecord last updated Apr 15, 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.