Submissions for variant NM_001009944.3(PKD1):c.1722+2T>C

dbSNP: rs886041836

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000357923	SCV000330604	pathogenic	not provided	2016-06-23	criteria provided, single submitter	clinical testing	The c.1722+2T>C pathogenic variant in the PKD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 8. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1722+2T>C variant was not observed in approximately 6300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Another variant at the same splice site, c.1722+1G>A, has been reported in association with autosomal dominant polycystic kidney disease, supporting the functional importance of this region of the protein (Audrézet et al., 2012). We interpret c.1722+2T>C as a pathogenic variant.
Fulgent Genetics, Fulgent Genetics	RCV002500972	SCV002813936	likely pathogenic	Polycystic kidney disease, adult type	2022-03-08	criteria provided, single submitter	clinical testing