ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.9866G>T (p.Ser3289Ile)

gnomAD frequency: 0.00287  dbSNP: rs148932323
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153703 SCV000203261 benign not specified 2016-04-06 criteria provided, single submitter clinical testing
Counsyl RCV000169100 SCV000220290 likely benign Autosomal recessive polycystic kidney disease 2014-05-01 criteria provided, single submitter literature only
Invitae RCV000169100 SCV000255211 benign Autosomal recessive polycystic kidney disease 2024-01-31 criteria provided, single submitter clinical testing
GeneDx RCV000489179 SCV000577808 likely benign not provided 2020-10-02 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 15805161, 21228398, 15108277)
Genetic Services Laboratory, University of Chicago RCV000153703 SCV000596429 likely benign not specified 2016-08-23 criteria provided, single submitter clinical testing
Mendelics RCV000169100 SCV001137137 benign Autosomal recessive polycystic kidney disease 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000489179 SCV001154766 likely benign not provided 2022-11-01 criteria provided, single submitter clinical testing PKHD1: BS2
Illumina Laboratory Services, Illumina RCV000169100 SCV001323267 uncertain significance Autosomal recessive polycystic kidney disease 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.
Genome-Nilou Lab RCV001449953 SCV001653484 uncertain significance Polycystic kidney disease 4 2021-05-18 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000489179 SCV001714168 uncertain significance not provided 2020-05-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001292034 SCV001480651 benign Polycystic kidney disease no assertion criteria provided clinical testing The PKHD1 p.Ser3289Ile variant was identified in 1 of 118 proband chromosomes (freq: 0.008) of individuals with autosomal recessive polycystic kidney disease (Sharp 2005). The variant was identified in dbSNP (rs148932323) as “with likely pathogenic allele”, ClinVar (interpreted as "likely benign" by Counsyl and 1 other, "benign" by Invitae and 1 other and "likely pathogenic" by GeneDx) and LOVD 3.0 (observed 6x). The variant was identified in control databases in 871 of 275,506 chromosomes (3 homozygous) at a frequency of 0.003 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 26 of 23,974 chromosomes (freq: 0.001), Other in 29 of 6406 chromosomes (freq: 0.005), Latino in 83 of 34,232 chromosomes (freq: 0.002), European in 599 of 125770 chromosomes (freq: 0.005), Ashkenazi Jewish in 1 of 10110 chromosomes (freq: 0.0001), Finnish in 120 of 25,664 chromosomes (freq: 0.004676), and South Asian in 13 of 30562 chromosomes (freq: 0.0005). The variant was not observed in the East Asian population. The p.Ser3289 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 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory criteria to be classified as benign. Assessment Date: 2019/08/09
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center RCV001844809 SCV001876969 uncertain significance Autosomal dominant polycystic liver disease 2021-09-01 no assertion criteria provided research
Natera, Inc. RCV000169100 SCV002075533 benign Autosomal recessive polycystic kidney disease 2017-06-30 no assertion criteria provided clinical testing

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