Submissions for variant NM_000322.5(PRPH2):c.499G>A (p.Gly167Ser)

dbSNP: rs527236098

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000438661	SCV000524231	pathogenic	not provided	2024-11-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22863181, 25474345, 34828423, 23049240, 18310263, 16024869, 23591405, 21269699, 32660024, 32531846, 38743414, 38219857, 25324289, 28559085, 32036094, 38474159, 35260635, 31213501, 35119454, 36460718, 36010202, 32531858, 34411390, 34996991, 37734845)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001055454	SCV001219847	pathogenic	PRPH2-related disorder	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 167 of the PRPH2 protein (p.Gly167Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant pattern dystrophy or retinitis pigmentosa (PMID: 16024869, 23591405, 25324289, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 143070). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PRPH2 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001073378	SCV001238919	pathogenic	Retinal dystrophy	2019-01-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000438661	SCV001246206	pathogenic	not provided	2019-02-01	criteria provided, single submitter	clinical testing
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250331	SCV001424651	likely pathogenic	Stargardt disease	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.499G>A in the PRPH2 gene has been previously studied(PMIDs 16024869, 22863181, 23591405, 25324289, 25474345, 28559085). We found this variant in 1 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (rs527236098,CM052911). It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PM5, PP1, PP3, PP5] and classified NM_000322.4:c.499G>A in the PRPH2 gene as a Likely Pathogenic mutation.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000438661	SCV001448002	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000438661	SCV004026291	pathogenic	not provided	2023-02-28	criteria provided, single submitter	clinical testing	PM1, PP3, PM5, PP4, PS4, PM2_SUP
Dept Of Ophthalmology, Nagoya University	RCV001073378	SCV004707353	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001073378	SCV005068445	likely pathogenic	Retinal dystrophy	2022-01-01	criteria provided, single submitter	clinical testing
Department of Ophthalmology and Visual Sciences Kyoto University	RCV000132579	SCV000172522	pathogenic	Retinitis pigmentosa		no assertion criteria provided	not provided	Converted during submission to Pathogenic.
Leiden Open Variation Database	RCV000438661	SCV001744954	pathogenic	not provided	2021-06-19	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters, Yoshito Koyanagi.