Submissions for variant NM_182914.3(SYNE2):c.12673C>T (p.Pro4225Ser)

gnomAD frequency: 0.00082  dbSNP: rs149296737

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000380064	SCV000333537	uncertain significance	not provided	2015-07-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001086857	SCV000387488	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086857	SCV000648825	likely benign	Emery-Dreifuss muscular dystrophy 5, autosomal dominant	2023-10-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021102	SCV003539219	uncertain significance	not specified	2022-05-26	criteria provided, single submitter	clinical testing	The c.12673C>T (p.P4225S) alteration is located in exon 66 (coding exon 65) of the SYNE2 gene. This alteration results from a C to T substitution at nucleotide position 12673, causing the proline (P) at amino acid position 4225 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000380064	SCV004134255	benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	SYNE2: BS1, BS2
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000380064	SCV001928361	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000380064	SCV001951937	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003909927	SCV004718745	likely benign	SYNE2-related disorder	2023-07-07	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).