Submissions for variant NM_001009944.3(PKD1):c.8118C>T (p.Thr2706=)

gnomAD frequency: 0.00033  dbSNP: rs375408086

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV002490825	SCV002800223	likely benign	Polycystic kidney disease, adult type	2021-08-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003932802	SCV004755440	likely benign	PKD1-related condition	2020-02-20	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500152	SCV000592814	likely benign	not provided		no assertion criteria provided	clinical testing	The PKD1 p.Thr2706Thr variant was not identified in the literature nor was it identified in the Clinvitae, ClinVar, GeneInsight COGR, MutDB, ADPKD Mutation Database, PKD1-LOVD, and PKD1-LOVD 3.0 databases. The variant was identified in the dbSNP database (rs375408086) as “NA” and in the NHLBI GO Exome Sequencing Project in 2 of 8238 European American alleles, the Exome Aggregation Consortium database (March 14, 2016) in 8 of 17150 chromosomes (freq. 0.0005) in the following populations: European (Non-Finnish) in 5 of 6284 chromosomes (freq. 0.0008), South Asian in 2 of 7952 chromosomes (freq.0.0003), African in 1 of 1292 chromosomes (freq. 0.0008), increasing the likelihood this could be a low frequency benign variant. However we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The p.Thr2706Thr variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000500152	SCV002036034	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000500152	SCV002037768	likely benign	not provided		no assertion criteria provided	clinical testing