Submissions for variant NM_025137.4(SPG11):c.6258G>T (p.Leu2086=)

gnomAD frequency: 0.00781  dbSNP: rs150761878

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118406	SCV000152806	uncertain significance	not provided	2014-03-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000461243	SCV000391269	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000461243	SCV000557278	benign	Hereditary spastic paraplegia 11	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000609000	SCV000714007	benign	not specified	2017-10-31	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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000461243	SCV000745403	likely benign	Hereditary spastic paraplegia 11	2017-06-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000118406	SCV000844027	benign	not provided	2018-03-29	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847726	SCV002105748	likely benign	Hereditary spastic paraplegia	2021-11-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000118406	SCV002497771	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	SPG11: BP4, BP7, BS2
Ambry Genetics	RCV002362748	SCV002659494	likely benign	Inborn genetic diseases	2019-07-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000461243	SCV000733441	likely benign	Hereditary spastic paraplegia 11		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000461243	SCV000745905	likely benign	Hereditary spastic paraplegia 11	2017-01-04	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003915170	SCV004735707	benign	SPG11-related disorder	2019-06-15	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).