ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.395G>A (p.Arg132Gln)

gnomAD frequency: 0.00002  dbSNP: rs753892865
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Goettingen RCV001174528 SCV001245433 uncertain significance Neuronopathy, distal hereditary motor, type 7B criteria provided, single submitter clinical testing Although there are 7 individuals harbouring the DCTN1 variant c.395G>A in the gnomAD database and one individual in the ExAC database there is still little known about the penetrance of pathogenic DCTN1 mutations. To our knowledge, this mutation is not located within a functional domain of the protein. The affected nucleotide is highly conserved, the affected amino acid (considering 10 species) is moderately conserved and there is a small physicochemical difference between Arg and Gln. Prediction programs do not provide a clear computational verdict on the pathogenicity of this variant and its effect on the nearest splice site. ACMG criteria used for classification: PM2, PP3 (considering three pathogenic predictions from M-CAP, PolyPhen-2 and MutationTaster vs. one benign prediction from SIFT). Thus, this DCTN1 variant is classified by our Institute as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003769856 SCV004592834 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2023-11-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 132 of the DCTN1 protein (p.Arg132Gln). This variant is present in population databases (rs753892865, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 917518). 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. 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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