ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.1151_1152del (p.Glu384fs) (rs878855228)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226597 SCV000291521 pathogenic Legius syndrome 2018-08-17 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 7 of the SPRED1 mRNA (c.1151_1152delAG), causing a frameshift at codon 384 and creating a premature translational stop signal in the last exon of the SPRED1 mRNA (p.Glu384Glyfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the SPROUTY-related domain (SPR) responsible for translocation to the plasma membrane and interaction with the Raf protein. The SPR domain also mediates dimerization of Spred proteins (PMID: 15683364). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. A different frameshift mutation c.1149_1152del (p.Gly385Ilefs*20) has been observed in several individuals and families with Legius syndrome (PMID: 19920235, 19443465, 21089071, 17704776), which suggests a truncation in the last exon disrupts SPRED1 function and causes disease. For these reasons, this variant has been classified as Pathogenic.

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