Submissions for variant NM_000276.4(OCRL):c.940-11G>A

dbSNP: rs776743373

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000338582	SCV000329445	pathogenic	not provided	2020-12-16	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a marked reduction in phosphatase activity compared to controls (Montjean et al., 2015); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 28803024, 31676009, 16381338, 21031565, 25480730, 27229703, 25305077, 31031587)
Baylor Genetics	RCV001335218	SCV001528313	pathogenic	Dent disease type 2	2018-06-28	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant was reported previously as disease-causing [PMID: 16381338, 28803024]
Invitae	RCV001855052	SCV002240528	pathogenic	Lowe syndrome	2022-08-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in retention of 9 nucleotides in intron 10 and introduces a premature termination codon (PMID: 16381338, 28803024). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 279859). This variant has been observed in individuals with Lowe syndrome (PMID: 16381338, 25480730, 28803024). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the OCRL gene. It does not directly change the encoded amino acid sequence of the OCRL protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV002274006	SCV002559014	likely pathogenic	Neurodevelopmental delay		criteria provided, single submitter	clinical testing
Pediatric Nephrology (Iijima Lab), Kobe University Graduate School of Medicine	RCV000590981	SCV000583551	pathogenic	Dent disease type 2; Lowe syndrome	2017-07-13	no assertion criteria provided	clinical testing	9 bp of AACTCATAG insertion between Exon 10 and 11 was confirmed by RT-PCR as a result of activating a novel splicing acceptor site by both patient's sample and minigene assay.