ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.3215C>G (p.Ala1072Gly)

gnomAD frequency: 0.00005  dbSNP: rs780875333
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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 RCV000695826 SCV000824347 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2023-03-14 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 574007). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. This variant is present in population databases (rs780875333, gnomAD 0.005%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1072 of the DCTN1 protein (p.Ala1072Gly).
PreventionGenetics, part of Exact Sciences RCV003392533 SCV004120108 uncertain significance DCTN1-related disorder 2023-04-21 criteria provided, single submitter clinical testing The DCTN1 c.3215C>G variant is predicted to result in the amino acid substitution p.Ala1072Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0047% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-74590551-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003403614 SCV004121742 uncertain significance not specified 2023-10-17 criteria provided, single submitter clinical testing Variant summary: DCTN1 c.3215C>G (p.Ala1072Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248158 control chromosomes (gnomAD). 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.3215C>G in individuals affected with DCTN1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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