Submissions for variant NM_001009944.3(PKD1):c.8913T>C (p.Ala2971=)

gnomAD frequency: 0.03447  dbSNP: rs9926309

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000244989	SCV000305806	benign	not specified		criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000712666	SCV000843185	benign	not provided	2017-10-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000999983	SCV000885916	benign	Polycystic kidney disease, adult type	2020-06-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000712666	SCV001801131	likely benign	not provided	2021-05-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 9285784, 17574468, 22008521, 22383692)
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001291905	SCV000592829	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Ala2971Ala variant was identified in 5 of 698 proband chromosomes (frequency: 0.007) from individuals or families with ADPKD, and was not identified in 442 control chromosomes from healthy individuals (Bataille_2011, Garcia-Gonzalez_2007, Rossetti_2012). The variant was also identified in dbSNP (ID: rs9926309) “With NA allele”, in 1000 Genomes Project in 190 of 5013 chromosomes (frequency: 0.0379), and in the NHLBI GO Exome Sequencing Project (ESP) in 5 of 8580 European American and in 394 of 4390 African American alleles. In addition, the variant is identified in the Exome Aggregation Consortium database (March 14, 2016) in 1155 of 119736 chromosomes (freq. 0.01) in the following populations: African in 1053 (57 homozygous) of 10158 chromosomes (freq. 0.1037), other in 5 of 886 chromosomes (freq. 0.006), Latino in 65 of 11538 chromosomes (freq. 0.006), European (Non-Finnish) in 29 of 65418 chromosomes (freq. 0.0004), South Asian in 2 of 16504 chromosomes (freq. 0.0001), East Asian in 1 of 6610 chromosomes (freq. 0.0001) but was not seen in a Finish population, increasing the likelihood this could be a low frequency benign variant. The variant is also listed in GeneInsight COGR (classified as benign), and in ADPKD Mutation Database (6x as likely neutral). The p.Ala2971Ala 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. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000244989	SCV002035511	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000244989	SCV002037363	benign	not specified		no assertion criteria provided	clinical testing