ClinVar Miner

Submissions for variant NM_182914.3(SYNE2):c.3688G>A (p.Ala1230Thr)

dbSNP: rs1294862758
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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 RCV001234766 SCV001407425 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2022-11-08 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 961124). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. This variant has not been reported in the literature in individuals affected with SYNE2-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1230 of the SYNE2 protein (p.Ala1230Thr). This variant is present in population databases (no rsID available, gnomAD 0.0009%).
Neuberg Centre For Genomic Medicine, NCGM RCV001234766 SCV005042941 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant criteria provided, single submitter clinical testing The missense c.3688G>A p.Ala1230Thr variant in SYNE2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ala1230Thr variant is reported with an allele frequency of 0.0004% in the gnomAD exomes database and is novel not in any individuals in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Ala1230Thr in SYNE2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ala at position 1230 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS.

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