Submissions for variant NM_001034853.2(RPGR):c.2405_2406del (p.Glu802fs)

dbSNP: rs398122960

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000622673	SCV000743013	likely pathogenic	Inborn genetic diseases	2017-10-12	criteria provided, single submitter	clinical testing
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	RCV000076907	SCV000890876	pathogenic	Retinitis pigmentosa 3	2017-10-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001008073	SCV001167811	pathogenic	not provided	2022-04-13	criteria provided, single submitter	clinical testing	Also known as g.ORF15+652_653delAG using alternate nomenclature; Frameshift variant predicted to result in protein truncation, as the last 351 amino acids are replaced with 31 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25494902, 24938718, 24043777, 29190250, 30567410, 20021257, 27032803, 10932196, 22264887, 28322733, 18552978, 29785639, 31953110, 33355362, 31054281, 32000842, 32702353, 31047384, 30543658, 33090715, 33576794, 33946315, 24077912)
Blueprint Genetics	RCV001074955	SCV001240562	pathogenic	Retinal dystrophy	2017-08-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001008073	SCV001247427	pathogenic	not provided	2024-02-01	criteria provided, single submitter	clinical testing	RPGR: PP1:Strong, PVS1:Strong, PM2, PS4:Moderate
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001003195	SCV001950369	likely pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Glu802GlyfsTer32 variant in RPGR was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
3billion	RCV001807778	SCV002058832	likely pathogenic	Macular degeneration, X-linked atrophic	2022-01-03	criteria provided, single submitter	clinical testing	The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000091389). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae	RCV001854345	SCV002193247	pathogenic	Primary ciliary dyskinesia	2024-01-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu802Glyfs*32) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 351 amino acid(s) of the RPGR (ORF15) protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with retinitis pigmentosa (PMID: 10932196, 18552978, 20021257, 22264887, 25544989). It has also been observed to segregate with disease in related individuals. This variant is also known as g.ORF15+652_653delAG. ClinVar contains an entry for this variant (Variation ID: 91389). This variant disrupts a region of the RPGR (ORF15) protein in which other variant(s) (p.Leu1130Lysfs*13) have been determined to be pathogenic (PMID: 22264887; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV002286702	SCV002577559	pathogenic	X-linked cone-rod dystrophy 1	2022-02-09	criteria provided, single submitter	clinical testing	PVS1, PM2, PP5
MGZ Medical Genetics Center	RCV002286702	SCV002581667	pathogenic	X-linked cone-rod dystrophy 1	2022-08-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV001008073	SCV002759652	pathogenic	not provided	2016-08-29	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498372	SCV002811517	pathogenic	X-linked cone-rod dystrophy 1; Retinitis pigmentosa 3; Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness; Macular degeneration, X-linked atrophic	2021-09-22	criteria provided, single submitter	clinical testing
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV001003195	SCV004030310	pathogenic	Retinitis pigmentosa	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Dept Of Ophthalmology, Nagoya University	RCV001074955	SCV004707081	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
OMIM	RCV000076907	SCV000030807	pathogenic	Retinitis pigmentosa 3	2000-08-01	no assertion criteria provided	literature only
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003195	SCV001161272	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research