ClinVar Genomic variation as it relates to human health
NM_000297.4(PKD2):c.1094+1G>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_000297.4(PKD2):c.1094+1G>A
Variation ID: 280008 Accession: VCV000280008.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q22.1 4: 88038502 (GRCh38) [ NCBI UCSC ] 4: 88959654 (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 Dec 6, 2016 Jan 15, 2023 Dec 28, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000297.4:c.1094+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NC_000004.12:g.88038502G>A NC_000004.11:g.88959654G>A NG_008604.1:g.35835G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000004.12:88038501:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- sequence_variant_affecting_splicing Sequence Ontology [SO:1000071]
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
781 | 1004 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 28, 2022 | RCV000379740.4 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Apr 22, 2022 | RCV001095620.8 | |
Pathogenic (1) |
no assertion criteria provided
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- | RCV001292116.2 |
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
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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
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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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Pathogenic
(Feb 05, 2020)
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criteria provided, single submitter
Method: research
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Polycystic kidney disease 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Cavalleri Lab, Royal College of Surgeons in Ireland
Accession: SCV001251257.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
PVS1, PM2, PP3, PP4, PP5
Clinical Features:
Polycystic kidney dysplasia (present)
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Pathogenic
(Mar 25, 2020)
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criteria provided, single submitter
Method: clinical testing
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Polycystic kidney disease 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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University of Iowa Renal Genetics Clinic, University of Iowa
Accession: SCV001250667.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This PKD2 gene variant alters a canonical splice site and has been previously reported in two individuals with autosomal dominant polycystic kidney disease (Chung 2006). … (more)
This PKD2 gene variant alters a canonical splice site and has been previously reported in two individuals with autosomal dominant polycystic kidney disease (Chung 2006). This variant was also shown to segregate with polycystic kidney disease in two affected relatives. It meets the following ACMG pathogenicity criteria; PVS1, PM2, PP3, PP5. (less)
Observation 1:
Clinical Features:
Polycystic kidney disease (present)
Age: 20-29 years
Sex: male
Ethnicity/Population group: Caucasian
Geographic origin: United States
Testing laboratory: Molecular Otolaryngology and Renal Research Laboratories
Date variant was reported to submitter: 2019-11-19
Testing laboratory interpretation: Pathogenic
Observation 2:
Clinical Features:
Polycystic kidney disease (present) , Stage 4 chronic kidney disease (present)
Age: 60-69 years
Sex: male
Ethnicity/Population group: Caucasian
Geographic origin: United States
Testing laboratory: Molecular Otolaryngology and Renal Research Laboratories
Date variant was reported to submitter: 2020-03-12
Testing laboratory interpretation: Pathogenic
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Pathogenic
(Feb 26, 2021)
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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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Athena Diagnostics Inc
Accession: SCV001879467.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. This variant has not been reported in large, multi-ethnic … (more)
This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. (less)
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Pathogenic
(Apr 22, 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: SCV001752518.2
First in ClinVar: Jul 18, 2021 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 28, 2022)
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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: SCV000329711.7
First in ClinVar: Dec 06, 2016 Last updated: Jan 15, 2023 |
Comment:
Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; … (more)
Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22863349, 27366664, 22508176, 31514750, 25525159, 33454723, 31328266, 35778421, 17100995) (less)
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Pathogenic
(Dec 09, 2019)
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no assertion criteria provided
Method: clinical testing
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Polycystic kidney disease 2
Affected status: yes
Allele origin:
germline
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Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV001468131.1
First in ClinVar: Jan 05, 2021 Last updated: Jan 05, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Polycystic Kidney disease
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: SCV001480948.1 First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Comment:
The PKD2 c.1094+1G>A variant was identified in 3 of 622 proband chromosomes (frequency: 0.005) from individuals or families with ADPKD (Chung 2006, Hwang 2016). The … (more)
The PKD2 c.1094+1G>A variant was identified in 3 of 622 proband chromosomes (frequency: 0.005) from individuals or families with ADPKD (Chung 2006, Hwang 2016). The variant was also identified in dbSNP (ID: rs58606740) as “With Pathogenic allele”, ClinVar (1x as pathogenic by GeneDx), LOVD 3.0 (1x), ADPKD Mutation Database (as definitely pathogenic). The variant was not identified in PKD2-LOVD. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). In addition the variant was found to segregate in 2 individuals from Korean families with ADPKD (Chung 2006). The c.1094+1G>A variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, 4 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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sequence_variant_affecting_splicing
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University of Iowa Renal Genetics Clinic, University of Iowa
Accession: SCV001250667.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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TRPP2 dysfunction decreases ATP-evoked calcium, induces cell aggregation and stimulates proliferation in T lymphocytes. | Magistroni R | BMC nephrology | 2019 | PMID: 31514750 |
PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data. | Entezam M | Kidney research and clinical practice | 2016 | PMID: 27366664 |
Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. | Audrézet MP | Human mutation | 2012 | PMID: 22508176 |
PKD2 gene mutation analysis in Korean autosomal dominant polycystic kidney disease patients using two-dimensional gene scanning. | Chung W | Clinical genetics | 2006 | PMID: 17100995 |
Text-mined citations for rs58606740 ...
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.