Submissions for variant NM_001009944.3(PKD1):c.11976C>G (p.Ala3992=)

gnomAD frequency: 0.00329  dbSNP: rs112387277

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000252377	SCV000305687	likely benign	not specified		criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000712585	SCV000843101	benign	not provided	2018-04-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001001863	SCV001159580	benign	Polycystic kidney disease, adult type	2019-05-24	criteria provided, single submitter	clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research	RCV001254184	SCV001430157	benign	Autosomal dominant polycystic kidney disease	2019-01-01	criteria provided, single submitter	research
GeneDx	RCV000712585	SCV001817579	likely benign	not provided	2022-01-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 11967008, 10987650, 10200984)
CeGaT Center for Human Genetics Tuebingen	RCV000712585	SCV004010436	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	PKD1: BP4, BP7, BS2
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292420	SCV001480873	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Ala3992Ala variant was identified in 4 of 732 proband chromosomes (frequency: 0.005) from individuals or families with ADPKD (Badenas 1999, Perrichot 1999, Rossetti 2002). The variant was also identified in dbSNP (ID: rs112387277) as “With Likely benign allele”, Clinvitae (classified as likely benign), ClinVar (classified as likely benign by Prevention Genetics), ADPKD Mutation Database (classified as likely neutral), the 1000 Genomes Project in 4 of 5000 chromosomes (frequency: 0.0008), the NHLBI GO Exome Sequencing Project in 29 of 8486 European American and in 1 of 4288 African American alleles, the Exome Aggregation Consortium database (August 8th 2016) in 262 (1 homozygous) of 59468 chromosomes (freq. 0.004) in the following populations: European in 196 of 31204 chromosomes (freq. 0.006), Asian in 30 of 11894 chromosomes (freq. 0.003), Latino in 21 of 5190 chromosomes (freq. 0.004), Finnish in 8 of 2492 chromosomes (freq. 0.003), African in 7 of 4082 chromosomes (freq. 0.002), increasing the likelihood this could be a low frequency benign variant. The p.Ala3992Ala 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, 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	RCV000712585	SCV001932690	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000712585	SCV001968741	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000712585	SCV002036651	likely benign	not provided		no assertion criteria provided	clinical testing