ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.439C>T (p.Arg147Ter) (rs1324667543)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623030 SCV000741689 pathogenic Inborn genetic diseases 2016-07-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000760313 SCV000890168 pathogenic not provided 2018-11-19 criteria provided, single submitter clinical testing The R147X variant in the IGHMBP2 gene has been reported previously in association with spinal muscular atrophy with respiratory distress type 1 (SMARD1) in patients with a second IGHBMP2 pathogenic variant on the opposite allele (Grohmann et al., 2003; Jedrzejowska et al., 2014; San Millan et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R147X variant is observed in 1/9850 (0.01%) alleles in individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). We interpret R147X as a pathogenic variant.
Invitae RCV000806942 SCV000946966 pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg147*) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another IGHMBP2 variant in several individuals affected with autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1) (PMID: 14681881, 26709713, 24388491). ClinVar contains an entry for this variant (Variation ID: 521206). Loss-of-function variants in IGHMBP2 are known to be pathogenic (PMID: 14681881, 25439726, 25568292). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789338 SCV000928691 uncertain significance Autosomal dominant distal hereditary motor neuropathy no assertion criteria provided literature only

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