ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.2161G>A (p.Gly721Arg)

gnomAD frequency: 0.00003  dbSNP: rs780023355
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001305926 SCV001495280 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 721 of the RPGRIP1L protein (p.Gly721Arg). This variant is present in population databases (rs780023355, gnomAD 0.004%). 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: 1008568). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV002486191 SCV002787804 uncertain significance Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2021-12-16 criteria provided, single submitter clinical testing
GeneDx RCV003319462 SCV004024035 uncertain significance not provided 2023-02-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001835487 SCV002085701 uncertain significance Familial aplasia of the vermis 2021-06-24 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733240 SCV005350078 uncertain significance RPGRIP1L-related disorder 2024-03-27 no assertion criteria provided clinical testing The RPGRIP1L c.2161G>A variant is predicted to result in the amino acid substitution p.Gly721Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) 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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