ClinVar Miner

Submissions for variant NM_182914.3(SYNE2):c.8003T>G (p.Leu2668Trp)

gnomAD frequency: 0.00056  dbSNP: rs143558316
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000535160 SCV000387412 benign Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000535160 SCV000648979 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 2668 of the SYNE2 protein (p.Leu2668Trp). This variant is present in population databases (rs143558316, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SYNE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 313535). 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 disruptive. 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 RCV004021588 SCV003629200 uncertain significance not specified 2024-05-15 criteria provided, single submitter clinical testing The c.8003T>G (p.L2668W) alteration is located in exon 48 (coding exon 47) of the SYNE2 gene. This alteration results from a T to G substitution at nucleotide position 8003, causing the leucine (L) at amino acid position 2668 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.