ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.529_533del (p.Ile177fs)

dbSNP: rs312262716
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000001169 SCV001139575 pathogenic Hereditary spastic paraplegia 11 2019-05-28 criteria provided, single submitter clinical testing
DASA RCV000001169 SCV002061250 pathogenic Hereditary spastic paraplegia 11 2022-01-05 criteria provided, single submitter clinical testing The c.529_533del;p.(Ile177Serfs*2) is a null frameshift variant (NMD) in the SPG11 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevantexon to the transcript -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 1110; OMIM: 610844.0002; PMID: 26556829; 19105190; 17322883) - PS4. The variant is present at low allele frequencies population databases (rs312262716– gnomAD 0.0006568%; ABraOM 0.000427 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Ile177Serfs*2) was detected in trans with a pathogenic variant (PMID: 26556829; 19105190) - PM3. The variant co-segregated with disease in multiple affected family members (PMID: 26556829; 19105190) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000001169 SCV002194060 pathogenic Hereditary spastic paraplegia 11 2024-02-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile177Serfs*2) 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: 17322883). ClinVar contains an entry for this variant (Variation ID: 1110). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000001169 SCV002762892 pathogenic Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing
GeneDx RCV004719605 SCV005326139 pathogenic not provided 2023-06-12 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: 19105190, 22696581, 29946510, 26556829, 17322883, 33059505)
OMIM RCV000001169 SCV000021319 pathogenic Hereditary spastic paraplegia 11 2015-11-10 no assertion criteria provided literature only
GeneReviews RCV000001169 SCV000058160 not provided Hereditary spastic paraplegia 11 no assertion provided literature only
OMIM RCV000202378 SCV000257389 pathogenic Charcot-Marie-Tooth disease axonal type 2X 2015-11-10 no assertion criteria provided literature only

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