Submissions for variant NM_002180.2(IGHMBP2):c.1064C>T (p.Ala355Val) (rs142062146)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001087969	SCV000642294	likely benign	Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S	2019-12-31	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000727033	SCV000705058	uncertain significance	not provided	2017-01-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000596269	SCV000728569	likely benign	not specified	2017-12-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000727033	SCV001148360	uncertain significance	not provided	2019-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV000596269	SCV001159710	uncertain significance	not specified	2018-07-12	criteria provided, single submitter	clinical testing	The IGHMBP2 c.1064C>T; p.Ala355Val variant (rs142062146) is reported in the literature in the homozygous state in an individual who was affected with schizophrenia or schizoaffective disorder; however, the contribution of this variant to the phenotype is not known (Need 2012). This variant is reported in ClinVar (Variation ID: 466572) and is found in the African population with an overall allele frequency of 0.73% (175/24,020 alleles) in the Genome Aggregation Database. The alanine at codon 355 is highly conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, the clinical significance of this variant is uncertain at this time.
Illumina Clinical Services Laboratory,Illumina	RCV001109641	SCV001267002	likely benign	Spinal muscular atrophy, distal, autosomal recessive, 1	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001174193	SCV001337319	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing