ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.6739_6742del (p.Glu2247fs)

dbSNP: rs312262782
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000034249 SCV000545194 pathogenic Hereditary spastic paraplegia 11 2024-07-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2247Leufs*14) 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 present in population databases (rs312262782, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with hereditary spastic paraplegia (PMID: 18079167, 20301389, 20571989, 23443022, 26556829). ClinVar contains an entry for this variant (Variation ID: 41348). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000493252 SCV000583291 pathogenic not provided 2022-11-19 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20571989, 18079167, 26556829, 20390432, 31980526, 27016404, 35572931)
Department of Biochemistry, Faculty of Medicine, University of Khartoum RCV000034249 SCV002573705 pathogenic Hereditary spastic paraplegia 11 criteria provided, single submitter research Found in trans with another loss-of-function variant
Ambry Genetics RCV002362609 SCV002666952 pathogenic Inborn genetic diseases 2022-04-15 criteria provided, single submitter clinical testing The c.6739_6742delGAGT pathogenic mutation, located in coding exon 36 of the SPG11 gene, results from a deletion of 4 nucleotides at nucleotide positions 6739 to 6742, causing a translational frameshift with a predicted alternate stop codon (p.E2247Lfs*14). This alteration has been detected as compound heterozygous or homozygous in multiple unrelated individuals with SPG11-related neurologic disorders (Stevanin G et al. Brain, 2008 Mar;131:772-84; de Bot ST et al. Eur J Hum Genet, 2013 Nov;21:1312-5; Denora PS et al. Brain, 2016 06;139:1723-34; Montecchiani C et al. Brain, 2016 Jan;139:73-85). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Genome-Nilou Lab RCV000034249 SCV002763674 pathogenic Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002490455 SCV002793437 pathogenic Amyotrophic lateral sclerosis type 5; Hereditary spastic paraplegia 11; Charcot-Marie-Tooth disease axonal type 2X 2021-12-08 criteria provided, single submitter clinical testing
GeneReviews RCV000034249 SCV000058189 not provided Hereditary spastic paraplegia 11 no assertion provided literature only

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