Submissions for variant NM_001009944.3(PKD1):c.9924-11C>T

gnomAD frequency: 0.00111  dbSNP: rs201154266

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001751555	SCV001987805	likely benign	not provided	2021-10-28	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001751555	SCV005217033	likely benign	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001729839	SCV006073899	likely benign	not specified	2025-04-25	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292256	SCV001480891	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 c.9924-11C>T variant was not identified in the literature nor was it identified in the ClinVar, LOVD 3.0, ADPKD Mutation Database, or the PKD1-LOVD database. The variant was identified in control databases in 197 of 174668 chromosomes at a frequency of 0.001, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 8 of 15394 chromosomes (freq: 0.0005), Other in 7 of 4722 chromosomes (freq: 0.001), Latino in 26 of 24734 chromosomes (freq: 0.001), European in 116 of 69022 chromosomes (freq: 0.002), Ashkenazi Jewish in 1 of 8398 chromosomes (freq: 0.0001), Finnish in 29 of 17870 chromosomes (freq: 0.001), and South Asian in 10 of 22782 chromosomes (freq: 0.0004); it was not observed in the East Asian population. The c.9924-11C>T variant is located in the 3' splice region; it does not affect the invariant -1 and -2 positions, although positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. However, 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	RCV001729839	SCV001977880	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001729839	SCV001979391	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001751555	SCV002036769	likely benign	not provided		no assertion criteria provided	clinical testing