ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.75G>C (p.Trp25Cys)

gnomAD frequency: 0.00024  dbSNP: rs146686238
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001064940 SCV001229877 uncertain significance PRPH2-related disorder 2023-04-10 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PRPH2 protein function. ClinVar contains an entry for this variant (Variation ID: 858947). This missense change has been observed in individual(s) with clinical features of PRPH2-related conditions (PMID: 22863181, 32531846). This variant is present in population databases (rs146686238, gnomAD 0.1%). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 25 of the PRPH2 protein (p.Trp25Cys).
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250339 SCV001424659 uncertain significance Retinitis pigmentosa 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.75G>C in the PRPH2 gene has been previously studied(PMID 22863181). 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 (rs146686238,CM127070). It is present in gnomAD browser (AF 0.0000609). This variant is not already listed in ClinVar. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM2, PP3] and classified NM_000322.4:c.75G>C in the PRPH2 gene as a Variant of Uncertain Significance.
Leiden Open Variation Database RCV001530275 SCV001745030 uncertain significance not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters.

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