ClinVar Miner

Submissions for variant NM_000297.4(PKD2):c.2411G>A (p.Ser804Asn) (rs145343957)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000405309 SCV000343762 benign not specified 2016-07-11 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755622 SCV000604829 uncertain significance not provided 2017-09-12 criteria provided, single submitter clinical testing
Invitae RCV001084804 SCV000658972 benign Autosomal dominant polycystic kidney disease 2020-10-19 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001157152 SCV001318699 uncertain significance Polycystic kidney disease 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001292453 SCV001480999 uncertain significance Polycystic kidney disease no assertion criteria provided clinical testing The PKD2 p.Ser804Asn variant was identified in 1 of 404 proband chromosomes (frequency: 0.0025) from individuals or families with Autosomal Dominant PKD (Rossetti 2007). The variant was also identified in dbSNP (ID: rs145343957) as “With other allele”, in ClinVar (as benign by EGL Genetic Diagnostics and Invitae, and as uncertain significance by ARUP Laboratories), LOVD 3.0 (1x as "indeterminate"), and ADPKD Mutation Database. The variant was not identified in PKD1-LOVD. The variant was identified in control databases in 277 of 276842 chromosomes (1 homozygous) at a frequency of 0.001001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 179 of 24034 chromosomes (freq: 0.007), Other in 17 of 6460 chromosomes (freq: 0.003), Latino in 65 of 34394 chromosomes (freq: 0.002), European (Non-Finnish) in 16 of 126422 chromosomes (freq: 0.0001); it was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The mutation is located within the consensus kinase recognition sequence; a functional study showed the p.Ser804Asn variant abolished Ser801 phosphorylation, indicating its likely physiological significance, and this study therefore classified the variant as pathogenic (Streets 2010). The p.Ser804 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs 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. This variant is classified as a variant of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.