Submissions for variant NM_138694.4(PKHD1):c.449-15TTC[2]

dbSNP: rs545812620

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000180001	SCV000232334	benign	not specified	2014-12-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000233390	SCV000291334	likely benign	Autosomal recessive polycystic kidney disease	2025-01-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000180001	SCV000919999	benign	not specified	2018-07-12	criteria provided, single submitter	clinical testing	Variant summary: PKHD1 c.449-9_449-7delTTC alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. The variant allele was found at a frequency of 0.00096 in 121106 control chromosomes, predominantly at a frequency of 0.01 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.44 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.449-9_449-7delTTC in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001552716	SCV001773455	likely benign	not provided	2021-03-09	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002500514	SCV002807481	likely benign	Polycystic kidney disease 4	2021-08-03	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000233390	SCV002083406	benign	Autosomal recessive polycystic kidney disease	2017-11-15	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003947537	SCV004764146	benign	PKHD1-related disorder	2019-12-20	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).