Submissions for variant NM_001271208.2(NEB):c.11806-1G>A (rs886041851)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000277796	SCV000330628	pathogenic	not provided	2018-08-30	criteria provided, single submitter	clinical testing	The c.11806-1G>A variant in the NEB gene has been reported previously in the homozygous state in a fetus presenting with akinesia (Monies et al., 2017). This splice site variant destroys the canonical splice acceptor site in intron 78. It is predicted to cause abnormal gene splicing. The c.11806-1G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.11806-1G>A as a pathogenic variant.
Invitae	RCV001214721	SCV001386420	likely pathogenic	Nemaline myopathy 2	2019-05-13	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 78 of the NEB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous in an individual affected with fetal akinesia (PMID: 28600779). ClinVar contains an entry for this variant (Variation ID: 280692). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). 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.
Natera, Inc.	RCV001214721	SCV001459398	pathogenic	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing