Submissions for variant NM_000322.5(PRPH2):c.458AGA[1] (p.Lys154del)

dbSNP: rs61755786

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250324	SCV001424644	pathogenic	Stargardt disease	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.461_463delAGA in the PRPH2 gene has been previously studied(PMIDs 8240110, 25412400, 27365499). 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 (rs61755786). It is absent in gnomAD browser. It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PS4, PM2, PM4, PP1, PP5] and classified NM_000322.4:c.461_463delAGA in the PRPH2 gene as a Pathogenic mutation.
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250325	SCV001424645	pathogenic	Cone-rod dystrophy	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.461_463delAGA in the PRPH2 gene has been previously studied(PMIDs 8240110, 25412400, 27365499). 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 (rs61755786). It is absent in gnomAD browser. It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PS4, PM2, PM4, PP1, PP5] and classified NM_000322.4:c.461_463delAGA in the PRPH2 gene as a Pathogenic mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001379857	SCV001577740	pathogenic	PRPH2-related disorder	2024-11-19	criteria provided, single submitter	clinical testing	This variant, c.461_463del, results in the deletion of 1 amino acid(s) of the PRPH2 protein (p.Lys154del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of inherited retinal disease (PMID: 8240110; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13178). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects PRPH2 function (PMID: 27365499). This variant disrupts the p.Lys154 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been observed in individuals with PRPH2-related conditions (PMID: 26161267), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004814902	SCV005072706	pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
OMIM	RCV000014064	SCV000034311	pathogenic	Retinitis pigmentosa 7	1993-11-01	no assertion criteria provided	literature only
Retina International	RCV000084974	SCV000117110	not provided	not provided		no assertion provided	not provided
OMIM	RCV000149467	SCV000196111	pathogenic	Patterned macular dystrophy 1	1993-11-01	no assertion criteria provided	literature only
Leiden Open Variation Database	RCV000084974	SCV001745139	likely pathogenic	not provided	2021-05-21	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitters to LOVD: Andreas Laner, LOVD, Manon Peeters.