Submissions for variant NM_001271208.2(NEB):c.3255+1G>A (rs375628303)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000536181	SCV000791647	pathogenic	Nemaline myopathy 2	2017-05-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000519006	SCV000617717	pathogenic	not provided	2016-01-11	criteria provided, single submitter	clinical testing	The c.3255+1 G>A variant in the NEB gene has been reported in association with nemaline myopathy (Lehtokari et al., 2006; Lehtokari et al., 2014). This splice site variant in the destroys the canonical splice donor site in intron 32. 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
Invitae	RCV000536181	SCV000640776	pathogenic	Nemaline myopathy 2	2018-01-09	criteria provided, single submitter	clinical testing	This sequence change affects donor splice site in intron 32 of the NEB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs375628303, ExAC 0.02%). This variant has been reported in individuals affected with nemaline myopathy (PMID: 25205138, 16917880). This variant is also known as g.53437G>A in the literature. 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). For these reasons, this variant has been classified as Pathogenic.