ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.1551_1552del (p.Cys518fs)

dbSNP: rs312262730
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000034176 SCV000915679 uncertain significance Hereditary spastic paraplegia 11 2018-10-30 criteria provided, single submitter clinical testing The SPG11 c.1551_1552delTT (p.Cys518SerfsTer39) variant is a frameshift variant and is predicted to result in a premature truncation of the protein. The p.Cys518SerfsTer39 variant, also reported as p.Leu517ValfsTer16 in literature, has been reported in two studies, in which it is found in a total of three individuals with spastic paraplegia, including in two siblings in a compound heterozygous state, and in one in a heterozygous state in whom a second variant was not identified (Samaranch et al. 2008; Zhang et al. 2016). In one family, two affected siblings presented with autosomal recessive hereditary spastic paraplegia with thin corpus callosum. The variant was absent from 100 Chinese control subjects. The p.Cys518SerfsTer39 variant is reported at a frequency of 0.000009 in the European (non-Finnish) population of the Genome Aggregation Database though this is based on one allele in a region of good sequence coverage, and so the variant is presumed to be rare. Based on the predicted truncating nature of the variant and limited evidence, the p.Cys518SerfsTer39 variants classified as a variant of unknown significance but suspicious for autosomal recessive spastic paraplegia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000034176 SCV004296963 pathogenic Hereditary spastic paraplegia 11 2024-01-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys518Serfs*39) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 18663179). This variant is also known as c.1550_1551delTT (p.L517fsX556). ClinVar contains an entry for this variant (Variation ID: 41275). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000034176 SCV000058114 not provided Hereditary spastic paraplegia 11 no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.