ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.11738G>A (p.Arg3913His)

gnomAD frequency: 0.00453  dbSNP: rs2661487
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228546 SCV000291324 benign Autosomal recessive polycystic kidney disease 2024-01-29 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000228546 SCV001323135 likely benign Autosomal recessive polycystic kidney disease 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV001557661 SCV001779459 likely benign not provided 2020-03-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002509333 SCV002819619 likely benign not specified 2022-12-16 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.11738G>A (p.Arg3913His) results in a non-conservative amino acid change in 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 0.0012 in 251238 control chromosomes, predominantly at a frequency of 0.016 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2.26 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 African or African-American origin. To our knowledge, no occurrence of c.11738G>A in individuals affected with Polycystic Kidney And Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=1) and likely benign (n=3). Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc. RCV000228546 SCV002075470 likely benign Autosomal recessive polycystic kidney disease 2017-05-11 no assertion criteria provided clinical testing

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