ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.2304G>A (p.Ser768=)

gnomAD frequency: 0.00011  dbSNP: rs770503381
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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 RCV001057766 SCV001222278 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-08-16 criteria provided, single submitter clinical testing This sequence change affects codon 768 of the RPGRIP1L mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RPGRIP1L protein. This variant also falls at the last nucleotide of exon 16, which is part of the consensus splice site for this exon. This variant is present in population databases (rs770503381, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with RPGRIP1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 853034). 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.
Natera, Inc. RCV001271275 SCV001452348 uncertain significance Familial aplasia of the vermis 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004545033 SCV004776316 uncertain significance RPGRIP1L-related disorder 2024-09-10 no assertion criteria provided clinical testing The RPGRIP1L c.2304G>A variant is not predicted to result in an amino acid change (p.=). This variant is predicted to impact splicing at the canonical splice donor site (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). This variant has been reported as a common polymorphism in a study of patients with Joubert syndrome related disorders (Brancati et al. 2008. PubMed ID: 18565097). This variant is reported in 0.039% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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