Submissions for variant NM_002180.2(IGHMBP2):c.2837G>A (p.Arg946Gln) (rs149824485)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236700	SCV000294162	uncertain significance	not provided	2017-10-19	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the IGHMBP2 gene. The R946Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R946Q variant is observed in 159/126,180 (0.1%) alleles from individuals of European background (Lek et al., 2016). The R946Q variant is a semi-conservative amino acidsubstitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina	RCV000292250	SCV000373811	uncertain significance	Spinal muscular atrophy, distal, autosomal recessive, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000556244	SCV000642353	likely benign	Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S	2019-12-19	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000236700	SCV001144479	likely benign	not provided	2019-02-27	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000236700	SCV001148364	uncertain significance	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173347	SCV001336435	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing