Submissions for variant NM_025137.4(SPG11):c.257+13G>A

gnomAD frequency: 0.00032  dbSNP: rs201936649

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000625162	SCV000391315	uncertain significance	Hereditary spastic paraplegia 11	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625162	SCV000743953	likely benign	Hereditary spastic paraplegia 11	2016-04-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000837894	SCV000979756	likely benign	not provided	2017-09-07	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000625162	SCV002448251	benign	Hereditary spastic paraplegia 11	2025-01-23	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000625162	SCV000745917	likely benign	Hereditary spastic paraplegia 11	2017-11-21	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000837894	SCV002034457	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003969884	SCV004781602	likely benign	SPG11-related disorder	2022-10-27	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).