Submissions for variant NM_000283.4(PDE6B):c.1920+2T>C

gnomAD frequency: 0.00001  dbSNP: rs763996159

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001091292	SCV001247228	pathogenic	not provided	2018-08-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001449717	SCV001652973	uncertain significance	not specified	2020-06-11	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Pathogenic. The c.1920+2T>C variant in PDE6B has been reported in the homozygous state in 4 siblings with retinitis pigmentosa; however parental testing was either not performed or not reported (Neveling 2012 PMID:22334370). This variant has also been identified in 0.002% (2/113282) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant occurs within the canonical splice site (+/- 1,2). However, computational tools are conflicting in their predictions for a splicing impact. In summary, while there is suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: PP1, PM2, PVS1_Moderate.
Clinical Genetics, Academic Medical Center	RCV001091292	SCV001917901	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001091292	SCV001954307	pathogenic	not provided		no assertion criteria provided	clinical testing