Submissions for variant NM_001009944.3(PKD1):c.6606G>A (p.Ala2202=)

gnomAD frequency: 0.00039  dbSNP: rs367600795

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000247249	SCV000305766	benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756500	SCV000884331	benign	not provided	2017-05-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000756500	SCV001871028	likely benign	not provided	2021-02-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 17574468)
Athena Diagnostics Inc	RCV000247249	SCV001879448	benign	not specified	2021-05-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756500	SCV004142862	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	PKD1: BP4, BP7
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292510	SCV001480643	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Ala2202Ala variant was not identified in the literature nor was it identified in the GeneInsight-COGR, LOVD 3.0, PKD1-LOVD, databases. The variant was also identified in dbSNP (ID: rs367600795) as “with benign allele”, in ClinVar as benign by Prevention Genetics; in the ADPKD Mutation Database 2X as likely neutral. The variant was identified in the NHLBI GO Exome Sequencing Project in 4 of 8290 European American alleles and in the control databases in 115 of 231474 chromosomes at a frequency of 0.0005 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). Furthermore, the variant was identified in the Ashkenazi Jewish population at a frequency greater than 1%: in 95 of 9208 chromosomes (freq: 0.01). 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.Ala2202Ala 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, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified in one individual by our laboratory with a co-occurring pathogenic variant (PKD2, c.1716+2T>A increasing the likelihood this variant does not have clinical significance. In summary, based on the above information this variant meets our laboratory criteria to be classified as benign. References (PMIDs): N/A