Submissions for variant NM_001009944.3(PKD1):c.4221G>A (p.Pro1407=)

gnomAD frequency: 0.00001  dbSNP: rs776410570

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV002486096	SCV002801147	likely benign	Polycystic kidney disease, adult type	2022-01-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292042	SCV001480684	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Pro1407= variant was not identified in the literature nor was it identified in the ClinVar, LOVD 3.0, ADPKD Mutation Database, or PKD1-LOVD databases. The variant was identified in dbSNP (ID: rs776410570). The variant was identified in control databases in 6 of 274530 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 23736 chromosomes (freq: 0.00004), Latino in 1 of 34410 chromosomes (freq: 0.00003), European in 2 of 124530 chromosomes (freq: 0.00002), East Asian in 1 of 18832 chromosomes (freq: 0.00005), and South Asian in 1 of 30774 chromosomes (freq: 0.00003), while the variant was not observed in the Other, Ashkenazi Jewish, or Finnish populations. In addition, we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The p.Pro1407= 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. 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.
PreventionGenetics, part of Exact Sciences	RCV003928827	SCV004737493	likely benign	PKD1-related disorder	2019-10-03	no assertion criteria provided	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).