ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.1505G>A (p.Arg502His)

gnomAD frequency: 0.00001  dbSNP: rs780066070
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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 RCV001896003 SCV002157381 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2024-11-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 502 of the DCTN1 protein (p.Arg502His). This variant is present in population databases (rs780066070, 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: 1384445). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DCTN1 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV003166918 SCV003863553 uncertain significance Inborn genetic diseases 2023-04-28 criteria provided, single submitter clinical testing The c.1505G>A (p.R502H) alteration is located in exon 14 (coding exon 14) of the DCTN1 gene. This alteration results from a G to A substitution at nucleotide position 1505, causing the arginine (R) at amino acid position 502 to be replaced by a histidine (H). Based on data from gnomAD, the A allele has an overall frequency of 0.002% (5/251300) total alleles studied. The highest observed frequency was 0.006% (1/16254) of African alleles. This amino acid position is well conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004801076 SCV005422769 uncertain significance not specified 2024-10-17 criteria provided, single submitter clinical testing Variant summary: DCTN1 c.1505G>A (p.Arg502His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251300 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1505G>A in individuals affected with Neuronopathy, distal hereditary motor, type 7B and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1384445). Based on the evidence outlined above, the variant was classified as uncertain significance.

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