ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.1235+894C>A

dbSNP: rs1202430946
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Undiagnosed Diseases Network, NIH RCV000626052 SCV000746672 pathogenic Charcot-Marie-Tooth disease axonal type 2S 2017-03-24 criteria provided, single submitter research This individual has been reported in PMID: 31020813.
GeneDx RCV002225695 SCV002504555 pathogenic not provided 2019-10-17 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss-of-function (Cassini et al., 2019); Observed in a patient in published literature with Charcot-Marie-Tooth phenotype with early onset symptoms (Cassini et al., 2019); This variant is associated with the following publications: (PMID: 31020813, 32190976)
Labcorp Genetics (formerly Invitae), Labcorp RCV003767835 SCV004578529 likely pathogenic Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S 2023-07-09 criteria provided, single submitter clinical testing Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 31020813). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 522869). This sequence change falls in intron 8 of the IGHMBP2 gene. It does not directly change the encoded amino acid sequence of the IGHMBP2 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 31020813, 32190976). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant.

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