Submissions for variant NM_001009944.3(PKD1):c.3295+1G>C

dbSNP: rs2092536130

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003128937	SCV003805272	pathogenic	not provided	2022-08-15	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 11857740)
Ambry Genetics	RCV004961192	SCV005475089	likely pathogenic	Inborn genetic diseases	2024-07-11	criteria provided, single submitter	clinical testing	The c.3295+1G>C intronic alteration consists of a G to C substitution one nucleotide after Intron 14 (C) of the PKD1 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was reported to segregate with disease in a family with features consistent with polycystic kidney disease; however, details were limited (McCluskey, 2002). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Based on the available evidence, this alteration is classified as likely pathogenic.