ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.127C>T (p.Arg43Ter) (rs200089714)

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
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000221711 SCV000271379 pathogenic Distal spinal muscular atrophy 2015-03-11 criteria provided, single submitter clinical testing The p.Arg43X variant in IGHMBP2 has been previously reported in one compound het erozygous individual with spinal muscular atrophy with respiratory distress (SMA RD1; Pitt 2003). It has also been identified in 0.01% (5/66736) European chromos omes by the Exome Aggregation Consortium (http://exac.broadinstitute.org; dbSNP rs200089714). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Th is nonsense variant leads to a premature termination codon at position 43, which is predicted to lead to a truncated or absent protein. Complete loss of IGHMBP2 function is an established disease mechanism for SMARD1. In summary, this varia nt meets our criteria to be classified as pathogenic for SMARD1 in an autosomal recessive manner (www.partners.org/personalizedmedicine/lmm).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000482426 SCV000345519 pathogenic not provided 2016-09-20 criteria provided, single submitter clinical testing
GeneDx RCV000482426 SCV000565070 pathogenic not provided 2017-03-03 criteria provided, single submitter clinical testing The R43X variant in the IGHMBP2 gene has been reported previously in the compound heterozygous state with a second pathogenic variant in a patient with SMARD1 (Pitt et al., 2003). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R43X variant is observed in 5/66736 (0.007%) alleles from individuals of Non-Finnish European background in large population cohorts the ExAC dataset (Lek et al., 2016). We interpret R43X as a pathogenic variant.
Invitae RCV001059408 SCV001224032 pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2019-12-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg43*) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs200089714, ExAC 0.007%). This variant has been observed in individual(s) with severe infantile neuropathy with diaphragmatic weakness (PMID: 14506069). ClinVar contains an entry for this variant (Variation ID: 228355). Loss-of-function variants in IGHMBP2 are known to be pathogenic (PMID: 14681881). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000482426 SCV001249649 pathogenic not provided 2016-08-01 criteria provided, single submitter clinical testing

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.