Submissions for variant NM_138694.4(PKHD1):c.8581A>G (p.Ser2861Gly) (rs150925674)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000197457	SCV000252884	benign	Autosomal recessive polycystic kidney disease	2019-12-31	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000254142	SCV000315845	likely benign	not specified		criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000254142	SCV000331145	benign	not specified	2015-10-28	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000590788	SCV000699882	benign	not provided	2017-08-21	criteria provided, single submitter	clinical testing	Variant summary: The PKHD1 c.8581A>G (p.Ser2861Gly) variant involves the alteration of a non-conserved nucleotide and 2/3 in silico tools (SNPsandGO and Mutation Taster not captured due to low reliability index and p-value, respectively) predict a benign outcome for this variant. This variant was found in 1011/276778 control chromosomes, predominantly observed in the European (Finnish) subpopulation at a frequency of 0.019838 (509/25658). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic PKHD1 variant (0.0070711), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. The variant of interest has been reported in multiple affected individuals including individuals that were compound heterozygotes for two pathogenic variants, further supporting the variant of interest being in the benign spectrum. The reports of its occurence in cis with another pathogenic variant in patients with a confirmed second disease causing variation, provides further supporting evidence in favor of its benign outcome. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/benign." Taken together, this variant is classified as Benign.
SIB Swiss Institute of Bioinformatics	RCV000197457	SCV000803596	likely benign	Autosomal recessive polycystic kidney disease	2018-05-31	criteria provided, single submitter	curation	This variant is interpreted as a Likely Benign, for Polycystic kidney disease 4 with or without polycystic liver disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
Mendelics	RCV000197457	SCV001137139	benign	Autosomal recessive polycystic kidney disease	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000197457	SCV001323390	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.