ClinVar Miner

Submissions for variant NM_015087.5(SPART):c.68C>A (p.Ala23Asp) (rs753340463)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483605 SCV000574250 uncertain significance not provided 2017-03-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SPG20 gene. The A23D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A23D variant is observed in 22/11548 (0.2%) alleles from individuals of Latino background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A23D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants have not been reported in Human Gene Mutation Database in association with SPG20-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000692468 SCV000820293 uncertain significance Troyer syndrome 2018-02-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 23 of the SPG20 protein (p.Ala23Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is present in population databases (rs753340463, ExAC 0.2%). This variant has not been reported in the literature in individuals with SPG20-related disease. ClinVar contains an entry for this variant (Variation ID: 424442). 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 disruptive, 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.