ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.138T>A (p.Cys46Ter) (rs372000714)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255598 SCV000321772 pathogenic not provided 2018-08-28 criteria provided, single submitter clinical testing The C46X pathogenic variant in the IGHMBP2 gene has been reported previously in the compound heterozygous state with another pathogenic IGHMBP2 variant in at least one individual with infantile-onset distal spinal muscle atrophy type 1, and in several adults with progressive sensorimotor neuropathy who had no symptoms of respiratory distress (Cotterie et al., 2014; Schottman et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The C46X variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret C46X as a pathogenic variant.
GeneReviews RCV000192258 SCV000239906 pathogenic Charcot-Marie-Tooth disease 2015-04-30 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000790277 SCV000929681 uncertain significance Distal spinal muscular atrophy no assertion criteria provided literature only
Invitae RCV000550952 SCV000642304 pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2017-06-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys46*) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs372000714, ExAC 0.001%). This variant has been reported along with a second variant in individuals and families affected with spinal muscular atrophy with respiratory distress 1, Charcot-Marie-Tooth disease type 2, and axonal sensorimotor neuropathy (PMID: 14681881, 25439726, 25568292). ClinVar contains an entry for this variant (Variation ID: 162194). Loss-of-function variants in IGHMBP2 are known to be pathogenic (PMID: 15269181, 25568292, 25439726). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000149574 SCV000196550 pathogenic Charcot-Marie-Tooth disease, axonal, type 2S 2015-02-03 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.