Submissions for variant NM_001009944.3(PKD1):c.8109C>T (p.Thr2703=)

gnomAD frequency: 0.00411  dbSNP: rs149879790

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000242829	SCV000305785	likely benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000334	SCV001157061	benign	Polycystic kidney disease, adult type	2018-10-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001555655	SCV001777106	likely benign	not provided	2020-10-05	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292191	SCV001480915	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Thr2703= variant was not identified in the literature nor was it identified in the LOVD 3.0 or PKD1-LOVD databases. The variant was identified in dbSNP (ID: rs149879790) as "With Likely benign allele", ClinVar (classified as likely benign by PreventionGenetics), and ADPKD Mutation Database (as likely neutral by Athena Diagnostics). The variant was identified in control databases in 330 of 181400 chromosomes at a frequency of 0.002, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 180 of 15966 chromosomes (freq: 0.01), Other in 3 of 4834 chromosomes (freq: 0.0006), Latino in 12 of 25804 chromosomes (freq: 0.0005), European in 41 of 73996 chromosomes (freq: 0.0006), Ashkenazi Jewish in 6 of 8472 chromosomes (freq: 0.0007), Finnish in 86 of 15602 chromosomes (freq: 0.006), and South Asian in 2 of 23480 chromosomes (freq: 0.00009); it was not observed in the East Asian population. The p.Thr2703= variant is not expected to have clinical significance because it does not result in a change of amino acid and occurs at a non-highly conserved nucleotide at a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001555655	SCV002034188	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001555655	SCV002036718	likely benign	not provided		no assertion criteria provided	clinical testing