Total submissions: 12
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV000556244 | SCV006054438 | uncertain significance | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2023-09-01 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005238784 | SCV005884160 | likely benign | not specified | 2024-12-10 | criteria provided, single submitter | clinical testing | Variant summary: IGHMBP2 c.2837G>A (p.Arg946Gln) results in a conservative amino acid change located in the AN1-like Zinc finger (IPR000058) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00062 in 250540 control chromosomes, predominantly at a frequency of 0.0012 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.073 fold of the estimated maximal expected allele frequency for a pathogenic variant in IGHMBP2 causing Charcot-Marie-Tooth disease axonal type 2S phenotype (0.0011). To our knowledge, no occurrence of c.2837G>A in individuals affected with Charcot-Marie-Tooth disease axonal type 2S and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 246570). Based on the evidence outlined above, the variant was classified as likely benign. |
| ARUP Laboratories, |
RCV000236700 | SCV005878130 | uncertain significance | not provided | 2024-04-12 | criteria provided, single submitter | clinical testing | The IGHMBP2 c.2837G>A; p.Arg946Gln variant (rs149824485) is reported in a cohort of Charcot-Marie-Tooth disease (Volodarsky 2021). This variant is also reported in ClinVar (Variation ID: 246570). This variant is observed in the general population with an overall allele frequency of 0.06% (183/281926 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.089). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Volodarsky M et al. Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients. J Med Genet. 2021 Apr;58(4):284-288. PMID: 32376792. |
| Mayo Clinic Laboratories, |
RCV000236700 | SCV004226199 | uncertain significance | not provided | 2022-10-31 | criteria provided, single submitter | clinical testing | BP4 |
| Revvity Omics, |
RCV000236700 | SCV003813316 | uncertain significance | not provided | 2020-03-06 | 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. |
| Molecular Genetics Laboratory, |
RCV001173347 | SCV001336435 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Ce |
RCV000236700 | SCV001148364 | likely benign | not provided | 2024-11-01 | criteria provided, single submitter | clinical testing | IGHMBP2: BP4 |
| Athena Diagnostics | RCV000236700 | SCV001144479 | likely benign | not provided | 2019-02-27 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000556244 | SCV000642353 | likely benign | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2025-01-27 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
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. |
| Gene |
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) |