ClinVar Miner

Submissions for variant NM_025219.3(DNAJC5):c.491G>A (p.Arg164Lys) (rs762961919)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187333 SCV000240915 uncertain significance not provided 2013-11-07 criteria provided, single submitter clinical testing p.Arg164Lys (AGG>AAG): c.491 G>A in exon 4 of the DNAJC5 gene (NM_025219.2). The Arg164Lys missense change in the DNAJC5 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one positively charged amino acid for another at a position that is conserved in mammals but is not conserved in more distantly related species. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Arg164Lys is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000702501 SCV000831357 uncertain significance Neuronal ceroid lipofuscinosis 2018-03-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 164 of the DNAJC5 protein (p.Arg164Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs762961919, ExAC 0.02%). This variant has not been reported in the literature in individuals with DNAJC5-related disease. ClinVar contains an entry for this variant (Variation ID: 205376). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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