Submissions for variant NM_000322.5(PRPH2):c.715C>T (p.Gln239Ter)

dbSNP: rs61755814

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000085015	SCV000490744	pathogenic	not provided	2019-08-05	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9279751, 29555955, 30718709, 28559085, 31618092, 32531846)
CeGaT Center for Human Genetics Tuebingen	RCV000085015	SCV001249901	pathogenic	not provided	2019-04-01	criteria provided, single submitter	clinical testing
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250335	SCV001424655	pathogenic	Stargardt disease	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.715C>T in the PRPH2 gene has been previously studied(PMIDs 9279751, 28559085, 29555955, 31618092). We found this variant in 5 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (CM971290). It is absent in gnomAD browser. It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PVS1, PS4, PM2, PP1, PP5] and classified NM_000322.4:c.715C>T in the PRPH2 gene as a Pathogenic mutation.
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250336	SCV001424656	pathogenic	Patterned dystrophy of the retinal pigment epithelium	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.715C>T in the PRPH2 gene has been previously studied(PMIDs 9279751, 28559085, 29555955, 31618092). We found this variant in 5 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (CM971290). It is absent in gnomAD browser. It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PVS1, PS4, PM2, PP1, PP5] and classified NM_000322.4:c.715C>T in the PRPH2 gene as a Pathogenic mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001386136	SCV001586265	pathogenic	PRPH2-related disorder	2024-11-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln239*) in the PRPH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRPH2 are known to be pathogenic (PMID: 8111389, 8485575, 8485576, 8675410, 16916875, 17504850, 22863181, 25675413, 26061163, 27365499, 29555955, 33546218). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal dominant pattern dystrophy (PMID: 279751, 28559085, 29555955, 31618092). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 98703). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815035	SCV005070887	pathogenic	Retinal dystrophy	2022-01-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV004760371	SCV005368484	pathogenic	Choroidal dystrophy, central areolar 2	2023-10-25	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PS4_MOD,PM2_SUP
Retina International	RCV000085015	SCV000117151	not provided	not provided		no assertion provided	not provided
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787668	SCV000926658	likely pathogenic	Macular dystrophy	2018-04-01	no assertion criteria provided	research
Leiden Open Variation Database	RCV000085015	SCV001745104	pathogenic	not provided	2021-04-06	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters.