ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.9415G>T (p.Asp3139Tyr) (rs45503297)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153707 SCV000203265 likely benign not specified 2015-03-16 criteria provided, single submitter clinical testing
Counsyl RCV000169053 SCV000220213 likely benign Autosomal recessive polycystic kidney disease 2014-04-09 criteria provided, single submitter literature only
Invitae RCV000169053 SCV000262501 benign Autosomal recessive polycystic kidney disease 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000153707 SCV000315853 likely benign not specified criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000169053 SCV000743913 likely benign Autosomal recessive polycystic kidney disease 2017-02-01 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000169053 SCV000745353 likely benign Autosomal recessive polycystic kidney disease 2015-08-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000169053 SCV001327183 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Integrated Genetics/Laboratory Corporation of America RCV000153707 SCV001361892 benign not specified 2019-01-14 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.9415G>T (p.Asp3139Tyr) results in a non-conservative amino acid change located in the right handed beta helix domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0041 in 277424 control chromosomes, predominantly at a frequency of 0.0075 within the Finnish subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within Finnish control individuals in the gnomAD database is approximately 1.061 fold of the estimated maximal expected allele frequency for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease phenotype (0.0071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Finnish origin. c.9415G>T has been reported in the literature in individuals affected with Polycystic Kidney and Hepatic Disease (Bergmann_2005, Furu_2003, Gunay-Aygun_2010, Losekoot_2005, Onuchi_2002, rossetti_2003, Ward_2002), however, authors predominantly refer to the variant as a polymorphism. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.

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