ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.2611+1G>T (rs786205090)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000528403 SCV000642345 pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-12-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 13 of the IGHMBP2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Loss-of-function variants in IGHMBP2 are known to be pathogenic. This particular variant has been reported to segregate with spinal muscular atrophy with respiratory distress in a single affected family (PMID: 11528396). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000598811 SCV000709970 likely pathogenic not provided 2018-02-08 criteria provided, single submitter clinical testing The c.2611+1 G>T splice variant in the IGHMBP2 gene has been reported previously in the homozygous state in an individual with SMARD1 (Grohmann et al., 2001). The c.2611+1 G>T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This variant destroys the canonical splice donor site of intron 13. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, in the absence of RNA/functional studies the actual effect of this change is unknown. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
OMIM RCV000009688 SCV000029906 pathogenic Werdnig-Hoffmann disease 2001-09-01 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789975 SCV000929364 uncertain significance Autosomal dominant distal hereditary motor neuropathy no assertion criteria provided literature only

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