ClinVar Miner

Submissions for variant NM_182914.3(SYNE2):c.1463A>G (p.Lys488Arg)

gnomAD frequency: 0.00001  dbSNP: rs1437677917
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000537464 SCV000648853 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2024-12-16 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 488 of the SYNE2 protein (p.Lys488Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 470936). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782442 SCV005394770 uncertain significance not specified 2024-09-24 criteria provided, single submitter clinical testing Variant summary: SYNE2 c.1463A>G (p.Lys488Arg) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249382 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1463A>G in individuals affected with Autosomal Dominant Emery-Dreifuss Muscular Dystrophy 5 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 470936). Based on the evidence outlined above, the variant was classified as uncertain significance.

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