U.S. flag

An official website of the United States government

NM_000297.4(PKD2):c.595+1G>A AND Autosomal dominant polycystic kidney disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 23, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001385677.7

Allele description [Variation Report for NM_000297.4(PKD2):c.595+1G>A]

NM_000297.4(PKD2):c.595+1G>A

Gene:
PKD2:polycystin 2, transient receptor potential cation channel [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q22.1
Genomic location:
Preferred name:
NM_000297.4(PKD2):c.595+1G>A
HGVS:
  • NC_000004.12:g.88008329G>A
  • NG_008604.1:g.5662G>A
  • NG_172259.1:g.1032G>A
  • NG_172260.1:g.52G>A
  • NM_000297.4:c.595+1G>AMANE SELECT
  • NC_000004.11:g.88929481G>A
Links:
dbSNP: rs1578111778
NCBI 1000 Genomes Browser:
rs1578111778
Molecular consequence:
  • NM_000297.4:c.595+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Autosomal dominant polycystic kidney disease (ADPKD)
Identifiers:
MONDO: MONDO:0004691; MedGen: C0085413

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001585623Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 23, 2020) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease.

Rossetti S, Consugar MB, Chapman AB, Torres VE, Guay-Woodford LM, Grantham JJ, Bennett WM, Meyers CM, Walker DL, Bae K, Zhang QJ, Thompson PA, Miller JP, Harris PC; CRISP Consortium..

J Am Soc Nephrol. 2007 Jul;18(7):2143-60. Epub 2007 Jun 20.

PubMed [citation]
PMID:
17582161
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001585623.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change affects a donor splice site in intron 1 of the PKD2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PKD2 are known to be pathogenic (PMID: 17582161, 22863349). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with autosomal dominant polycystic kidney disease (PMID: 12707387, 22508176, 31740684). This variant is also known as IVS1+1G>A in the literature. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024