ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.6100C>T (p.Arg2034Ter) (rs118203963)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000001168 SCV000253955 pathogenic Spastic paraplegia 11, autosomal recessive 2015-03-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 2034 (p.Arg2034*). It is expected to result in an absent or disrupted protein product. Truncating variants in SPG11 are known to be pathogenic. This particular truncation has been reported in the literature in patients with autosomal recessive hereditary spastic paraplegia. (PMID: 17322883, 18332254, 18079167, 18663179, 19438933.). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000518418 SCV000615421 pathogenic not provided 2017-01-20 criteria provided, single submitter clinical testing
GeneDx RCV000518418 SCV000748243 pathogenic not provided 2018-05-08 criteria provided, single submitter clinical testing The R2034X nonsense variant in the SPG11 gene has been reported previously in the homozygous state in several unrelated patients with spastic paraplegia with thin corpus callosum (Stevanin et al., 2007). The R2034X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
OMIM RCV000001168 SCV000021318 pathogenic Spastic paraplegia 11, autosomal recessive 2015-11-10 no assertion criteria provided literature only
GeneReviews RCV000001168 SCV000058181 pathologic Spastic paraplegia 11, autosomal recessive 2013-01-31 no assertion criteria provided curation Converted during submission to Pathogenic.
OMIM RCV000202373 SCV000257388 pathogenic Charcot-Marie-Tooth disease, axonal type 2X 2015-11-10 no assertion criteria provided literature only
Baylor Genetics RCV000414837 SCV000328861 pathogenic Spastic paraplegia 11, autosomal recessive; Charcot-Marie-Tooth disease, axonal type 2X 2015-05-27 no assertion criteria provided clinical testing Our laboratory reported three molecular diagnoses in CA2 (NM_000067.2, c.232+1G>A), MCCC2 (NM_022132.4, c.1015G>A), and SPG11 (NM_025137.3, c.6100C>T) in one individual with clinical features of global developmental delay, developmental regression, autistic features, intellectual disability, hypotonia, ataxia, dysmorphic features, short stature, microcephaly, hyperextensibility, failure to thrive, structural brain abnormalities, skeletal abnormalities, and limb malformation. The CA2 variant has been previously reported as disease-causing [PMID 1301935]. Heterozygotes would be expected to be asymptomatic carriers.

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