ClinVar Miner

Submissions for variant NM_182914.3(SYNE2):c.16905+4A>C

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001068697 SCV001233824 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2019-11-22 criteria provided, single submitter clinical testing This sequence change falls in intron 92 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 (rs369093036, ExAC 0.002%). This variant has not been reported in the literature in individuals with SYNE2-related conditions. 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 is not likely to affect RNA splicing, 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.
Illumina Clinical Services Laboratory,Illumina RCV001068697 SCV001272453 uncertain significance 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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