ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.1756+4C>T

gnomAD frequency: 0.00003  dbSNP: rs778913429
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000548573 SCV000642321 uncertain significance Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S 2022-10-18 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the IGHMBP2 gene. It does not directly change the encoded amino acid sequence of the IGHMBP2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs778913429, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 466584). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000611337 SCV000727869 likely benign not specified 2018-02-28 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Mayo Clinic Laboratories, Mayo Clinic RCV001509412 SCV001716108 uncertain significance not provided 2020-01-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002413541 SCV002716585 uncertain significance Inborn genetic diseases 2020-03-12 criteria provided, single submitter clinical testing The c.1756+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 12 in the IGHMBP2 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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