Submissions for variant NM_000276.4(OCRL):c.1621C>T (p.Arg541Ter)

dbSNP: rs1182741031

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV004025269	SCV000741527	pathogenic	Nephrolithiasis/nephrocalcinosis	2023-08-23	criteria provided, single submitter	clinical testing	The c.1621C>T (p.R541*) alteration, located in exon 16 of the OCRL gene, consists of a C to T substitution at nucleotide position 1621. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 541. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in multiple individuals with clinical features consistent with Lowe syndrome (Hichri, 2011; Recker, 2015; Sinha, 2022; Sakakibara, 2022). Based on the available evidence, this alteration is classified as pathogenic.
Baylor Genetics	RCV000680054	SCV000807493	pathogenic	Lowe syndrome	2017-09-01	criteria provided, single submitter	clinical testing	This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory maternally inherieted in a 2-year-old male with global delays, sensorineural hearing loss, hypotonia, dysmorphisms, short stature, septo-optic dysplasia, bilateral cateracts, brain cyst, nephrocalcinosis/hypercalcemia, craniosynostosis, delayed bone age, undscended testes
Labcorp Genetics (formerly Invitae), Labcorp	RCV000680054	SCV002239503	pathogenic	Lowe syndrome	2023-02-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 521093). This premature translational stop signal has been observed in individual(s) with clinical features of Lowe syndrome (PMID: 25326635, 25480730). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg541*) in the OCRL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OCRL are known to be pathogenic (PMID: 19390221, 21031565, 22381590).
3billion	RCV000680054	SCV002318507	pathogenic	Lowe syndrome	2022-03-22	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant.It is not observed in the gnomAD v2.1.1 dataset. The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000521093, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand	RCV000680054	SCV004024493	pathogenic	Lowe syndrome	2023-07-01	criteria provided, single submitter	research