ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.425G>A (p.Arg142Gln)

gnomAD frequency: 0.00003  dbSNP: rs554945964
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486555 SCV000565429 uncertain significance not provided 2020-04-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28559085, 32531846)
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250321 SCV001424641 likely pathogenic Stargardt disease 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.425G>A in the PRPH2 gene has been previously studied(PMID 28559085). 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 (rs554945964; CM1723376). It is present in gnomAD browser (AF 0.00000406). It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PM5, PP3, PP5] and classified NM_000322.4:c.425G>A in the PRPH2 gene as a Likely Pathogenic mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV001302351 SCV001491556 likely pathogenic PRPH2-related disorder 2022-01-15 criteria provided, single submitter clinical testing 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: 418424). This missense change has been observed in individual(s) with autosomal dominant PRPH2-related conditions (PMID: 28559085, 32531846). This variant is present in population databases (rs554945964, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 142 of the PRPH2 protein (p.Arg142Gln). This variant disrupts the p.Arg142 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8644804, 19038374, 19243827, 28076437, 28559085). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Leiden Open Variation Database RCV000486555 SCV001745131 likely pathogenic not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters.

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