Submissions for variant NM_001009944.3(PKD1):c.3495C>T (p.Asp1165=)

gnomAD frequency: 0.00036  dbSNP: rs375384742

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757659	SCV000885960	benign	not provided	2018-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005407938	SCV006073933	likely benign	not specified	2025-04-25	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292085	SCV001480851	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Asp1165= variant was not identified in the literature nor was it identified in the ClinVar, ADPKD Mutation Database, or PKD1-LOVD databases. The variant was also identified in dbSNP (ID: rs375384742) and LOVD 3.0 (1x as likely benign). The variant was identified in control databases in 76 of 207638 chromosomes at a frequency of 0.0004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2 of 18136 chromosomes (freq: 0.0001), Other in 4 of 5212 chromosomes (freq: 0.0008), Latino in 4 of 27514 chromosomes (freq: 0.0002), European in 1 of 88368 chromosomes (freq: 0.00001), East Asian in 60 of 14396 chromosomes (freq: 0.004), and South Asian in 5 of 25332 chromosomes (freq: 0.0002); it was not observed in the Ashkenazi Jewish or Finnish populations. The p.Asp1165= 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000757659	SCV001932398	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000757659	SCV001967953	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003908071	SCV004718382	benign	PKD1-related disorder	2019-08-06	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).