Submissions for variant NM_138694.4(PKHD1):c.1234-5C>T

gnomAD frequency: 0.01262  dbSNP: rs116124750

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001084231	SCV000291326	benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000247240	SCV000315772	benign	not specified		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000585908	SCV000699848	likely benign	not provided	2016-04-26	criteria provided, single submitter	clinical testing	Variant summary: The variant of interest is located at a non-conserved intronic position, not widely known to affect splicing with 3/5 in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency 459/120956 (1/263 including 9 homozygotes), predominantly in the African cohort, 410/10276 (1/25 including 8 homozygotes), which exceeds the predicted maximum expected allele frequency for a pathogenic PKHD1 variant of 1/141. Therefore, suggesting that the variant of interest is a common polymorphism found in population(s) of African origin. The variant of interest has been found in affected individuals via publications, although with limited information (ie lack of co-occurrence and co-segregation data) and authors classify the variant as "polymorphism." In addition, a reputable clinical laboratory cites the variant with a "benign" classification. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as likely benign until additional information becomes available.
Illumina Laboratory Services, Illumina	RCV001084231	SCV001321983	likely benign	Autosomal recessive polycystic kidney disease	2018-01-13	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	RCV000585908	SCV001893683	benign	not provided	2021-02-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 15698423, 15805161)
Fulgent Genetics, Fulgent Genetics	RCV002494667	SCV002802162	likely benign	Polycystic kidney disease 4	2021-07-21	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001084231	SCV002081091	benign	Autosomal recessive polycystic kidney disease	2017-05-11	no assertion criteria provided	clinical testing