ClinVar Miner

Submissions for variant NM_006915.3(RP2):c.768G>C (p.Glu256Asp)

dbSNP: rs1227276668
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001376362 SCV001239530 likely pathogenic Retinitis pigmentosa 2 2020-08-14 criteria provided, single submitter clinical testing We have detected the RP2 c.768G>C, p.(Glu256Asp) previously in two male patients with retinal dystrophy ( BpG unpublished observations). Missense variants in nearby residues, Leu253Arg and Leu253Pro, have been reported in the HGMD Professional 2019.2 database in association with X-linked retinitis pigmentosa.
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376362 SCV001573479 uncertain significance Retinitis pigmentosa 2 2021-04-08 criteria provided, single submitter research The RP2 c.768G>C variant was identified in an individual with retinitis pigmentosa with a presumed X-linked inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002557901 SCV003205275 uncertain significance not provided 2024-08-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 256 of the RP2 protein (p.Glu256Asp). This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinal degeneration and/or retinitis pigmentosa (PMID: 34906470; internal). ClinVar contains an entry for this variant (Variation ID: 866167). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Dept Of Ophthalmology, Nagoya University RCV003890230 SCV004707145 uncertain significance Retinal dystrophy 2023-10-01 criteria provided, single submitter research
GeneDx RCV002557901 SCV005081114 uncertain significance not provided 2024-02-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); The last nucleotide of exon variant in a gene for which loss of function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 34906470)

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