ClinVar Miner

Submissions for variant NM_182914.2(SYNE2):c.14139+5G>A (rs374778697)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000305817 SCV000336375 uncertain significance not provided 2015-10-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000698569 SCV000387513 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.
Invitae RCV000698569 SCV000827241 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2018-02-12 criteria provided, single submitter clinical testing This sequence change falls in intron 75 of the SYNE2 gene. It does not directly change the encoded amino acid sequence of the SYNE2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs374778697, ExAC 0.02%). This variant has not been reported in the literature in individuals with SYNE2-related disease. ClinVar contains an entry for this variant (Variation ID: 283963). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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