Submissions for variant NM_002180.3(IGHMBP2):c.2837G>A (p.Arg946Gln)

gnomAD frequency: 0.00108  dbSNP: rs149824485

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236700	SCV000294162	uncertain significance	not provided	2022-11-28	criteria provided, single submitter	clinical testing	Reported in a single individual with CMT and classified as a variant of uncertain signficance by the authors; no information about patient phenotype or segregation was provided (Volodarsky et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32376792)
Illumina Laboratory Services, Illumina	RCV000292250	SCV000373811	uncertain significance	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, 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	Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S	2024-01-25	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000236700	SCV001144479	likely benign	not provided	2019-02-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000236700	SCV001148364	uncertain significance	not provided	2022-02-01	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
Ambry Genetics	RCV002436064	SCV002748456	uncertain significance	Inborn genetic diseases	2023-10-05	criteria provided, single submitter	clinical testing	The c.2837G>A (p.R946Q) alteration is located in exon 15 (coding exon 15) of the IGHMBP2 gene. This alteration results from a G to A substitution at nucleotide position 2837, causing the arginine (R) at amino acid position 946 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000236700	SCV003813316	uncertain significance	not provided	2020-03-06	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000236700	SCV004226199	uncertain significance	not provided	2022-10-31	criteria provided, single submitter	clinical testing	BP4