Submissions for variant NM_182914.3(SYNE2):c.17583G>T (p.Trp5861Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002472233	SCV002769332	uncertain significance	Emery-Dreifuss muscular dystrophy 5, autosomal dominant	2020-05-21	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v0.6.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease for this gene. 0104 - Mechanism of disease for this gene is dominant negative. 0107 - This gene is known to be associated with autosomal dominant disease. 0200 - Variant is predicted to result in a missense amino acid change from tryptophan to cysteine (exon 97). 0301 - Variant is present in gnomAD <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). 0501 - Missense variant consistently predicted to be damaging by in-silico tools or highly conserved with a major amino acid change. 0600 - Variant is located in an annotated domain or motif that does not have a well established function (SMC prok B superfamily domain; NCBI). 0705 - No comparable variants in relevant codon/region have previous evidence for pathogenicity. 0807 - Variant has not previously been reported in a clinical context. 0905 - No published segregation evidence has been identified for this variant. 1007 - No published functional evidence has been identified for this variant. 1205 - Variant is maternally inherited. Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Labcorp Genetics (formerly Invitae), Labcorp	RCV002472233	SCV004622660	uncertain significance	Emery-Dreifuss muscular dystrophy 5, autosomal dominant	2023-02-15	criteria provided, single submitter	clinical testing	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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1805815). This variant has not been reported in the literature in individuals affected with SYNE2-related conditions. This variant is present in population databases (rs767570119, gnomAD 0.0009%). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 5861 of the SYNE2 protein (p.Trp5861Cys).