Submissions for variant NM_138694.4(PKHD1):c.9492C>T (p.Ser3164=)

gnomAD frequency: 0.00084  dbSNP: rs17752991

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082593	SCV000114635	benign	not specified	2012-08-09	criteria provided, single submitter	clinical testing
Counsyl	RCV000169283	SCV000220590	likely benign	Autosomal recessive polycystic kidney disease	2014-08-14	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV000169283	SCV001000858	benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000169283	SCV001327182	likely benign	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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000082593	SCV001361897	benign	not specified	2019-02-15	criteria provided, single submitter	clinical testing	Variant summary: PKHD1 c.9492C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0018 in 282262 control chromosomes, predominantly within the East Asian subpopulation at a frequency of 0.018 in the gnomAD database, including 2 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2.5-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 East Asian origin. Moreover, the variant was also reported in Japanese healthy controls with a frequency of 0.0256 (including 2 homozygotes) that is approximately 3.6-fold higher than the estimated maximal expected allele frequency for a pathogenic PKHD1 variant, further supporting that the variant is a benign polymorphism found primarily in populations of East Asian origin (HGVD). c.9492C>T has also been reported in the literature in healthy control individuals (e.g. Furu 2003, Bergmann 2005). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001705805	SCV001812943	likely benign	not provided	2021-03-23	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000169283	SCV002077945	likely benign	Autosomal recessive polycystic kidney disease	2017-05-11	no assertion criteria provided	clinical testing