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	2019-07-20	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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