ClinVar Miner

Submissions for variant NM_182914.2(SYNE2):c.12695C>T (p.Pro4232Leu) (rs139959852)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000554298 SCV000648826 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 4232 of the SYNE2 protein (p.Pro4232Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs139959852, ExAC 0.02%). This variant has not been reported in the literature in individuals with a SYNE2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on SYNE2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000554298 SCV001268411 benign Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2018-01-13 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.

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