ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.2356del (p.Ala786fs)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Inherited Neuropathy Consortium RCV000790284 SCV000929688 uncertain significance Distal spinal muscular atrophy no assertion criteria provided literature only
Invitae RCV000800244 SCV000939944 pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-09-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala786Profs*45) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed on the opposite chromosome (in trans) from a likely pathogenic variant in an individual affected with spinal muscular atrophy with respiratory distress type I (SMARD1) (PMID: 16765827). This variant has also been observed in combination with another IGHMBP2 variant in other individuals affected with SMARD1 and Charcot-Marie-Tooth disease type 2 (PMID: 28397221, 28065684). These findings are consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as c.2355_2356delG in the literature. 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.

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