Submissions for variant NM_000322.5(PRPH2):c.612C>G (p.Tyr204Ter)

dbSNP: rs1554269081

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627208	SCV000748195	pathogenic	not provided	2017-02-15	criteria provided, single submitter	clinical testing	The Y204X nonsense variant in the PRPH2 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Blueprint Genetics	RCV001074257	SCV001239830	pathogenic	Retinal dystrophy	2019-05-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001389850	SCV001591368	pathogenic	PRPH2-related disorder	2023-06-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 523772). This premature translational stop signal has been observed in individual(s) with autosomal dominant inherited retinal disease (PMID: 29555955). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr204*) 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).
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001074257	SCV005068580	pathogenic	Retinal dystrophy	2021-01-01	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003144	SCV001161213	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research
Leiden Open Variation Database	RCV000627208	SCV001744976	pathogenic	not provided	2021-04-06	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitters to LOVD: Global Variome, with Curator vacancy, LOVD, Manon Peeters.