ClinVar Miner

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

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Total submissions: 5
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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 (; 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 (
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 2019-09-03 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 14506069)
Invitae RCV001059408 SCV001224032 pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2020-08-05 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

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