Submissions for variant NM_002180.3(IGHMBP2):c.1827G>A (p.Ala609=)

gnomAD frequency: 0.00003  dbSNP: rs541245852

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV004547634	SCV000308717	likely benign	IGHMBP2-related disorder	2019-04-05	criteria provided, single submitter	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).
Illumina Laboratory Services, Illumina	RCV000372286	SCV000373784	benign	Autosomal recessive distal spinal muscular atrophy 1	2018-01-12	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.
Invitae	RCV000526636	SCV000642325	benign	Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S	2024-01-31	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173373	SCV001336461	benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
GeneDx	RCV001651165	SCV001868396	benign	not provided	2018-07-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411118	SCV002715573	likely benign	Inborn genetic diseases	2019-07-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.