Submissions for variant NM_000322.5(PRPH2):c.515G>A (p.Arg172Gln)

dbSNP: rs61755793

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001054658	SCV001219004	pathogenic	PRPH2-related disorder	2024-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 172 of the PRPH2 protein (p.Arg172Gln). This variant is present in population databases (rs61755793, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal dominant macular dystrophy or central areolar choroidal dystrophy in families, albeit with incomplete penetrance (PMID: 8485576, 19038374, 19243827). It has also been observed to segregate with disease in related individuals. This variant is also known as RDS p.Arg172Gln. ClinVar contains an entry for this variant (Variation ID: 13167). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRPH2 protein function. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001074392	SCV001239970	pathogenic	Retinal dystrophy	2019-08-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000084982	SCV001249905	pathogenic	not provided	2017-11-01	criteria provided, single submitter	clinical testing
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250353	SCV001424674	pathogenic	Patterned dystrophy of the retinal pigment epithelium	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.515G>A in the PRPH2 gene has been previously studied(PMIDs 8485576, 22003107, 25082885, 27977834, 28559085, 29555955). We found this variant in 2 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (rs61755793,CM930637). It is present in gnomAD browser (AF 0.00000406). It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PS4, PP1-S, PM1, PM2, PP3, PP5] and classified NM_000322.4:c.515G>A in the PRPH2 gene as a Pathogenic mutation.
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250367	SCV001424700	pathogenic	Stargardt disease	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.515G>A in the PRPH2 gene has been previously studied(PMIDs 8485576, 22003107, 25082885, 27977834, 28559085, 29555955). We found this variant in 2 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (rs61755793,CM930637). It is present in gnomAD browser (AF 0.00000406). It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PS4, PP1-S, PM1, PM2, PP3, PP5] and classified NM_000322.4:c.515G>A in the PRPH2 gene as a Pathogenic mutation.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000084982	SCV001447858	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001799605	SCV002044448	pathogenic	Vitelliform macular dystrophy 3	2021-12-14	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PM5_STR, PP1_STR, PS4_MOD, PM2_SUP, PP3
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001074392	SCV005069765	likely pathogenic	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
OMIM	RCV000014053	SCV000034300	pathogenic	Choroidal dystrophy, central areolar 2	1993-03-01	no assertion criteria provided	literature only
Retina International	RCV000084982	SCV000117118	not provided	not provided		no assertion provided	not provided
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787663	SCV000926652	pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787664	SCV000926653	pathogenic	Macular dystrophy	2018-04-01	no assertion criteria provided	research
Leiden Open Variation Database	RCV000084982	SCV001744961	pathogenic	not provided	2021-04-06	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters.
Clinical Genetics, Academic Medical Center	RCV000084982	SCV001923785	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000084982	SCV001954752	likely pathogenic	not provided		no assertion criteria provided	clinical testing