Submissions for variant NM_025137.4(SPG11):c.6224A>G (p.Asn2075Ser)

gnomAD frequency: 0.00270  dbSNP: rs140824939

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000168174	SCV000218837	likely benign	Hereditary spastic paraplegia 11	2025-01-30	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000194672	SCV000249016	likely benign	not specified	2019-07-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000512885	SCV000608715	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	SPG11: BP4, BS2
Eurofins Ntd Llc (ga)	RCV000194672	SCV000709276	likely benign	not specified	2017-06-19	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000512885	SCV000844026	benign	not provided	2018-02-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000168174	SCV001273773	uncertain significance	Hereditary spastic paraplegia 11	2018-01-12	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.
GeneDx	RCV000512885	SCV001905230	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27066562)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847791	SCV002105747	likely benign	Hereditary spastic paraplegia	2022-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002362861	SCV002658187	likely benign	Inborn genetic diseases	2020-06-18	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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000194672	SCV002033932	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000512885	SCV002034485	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000512885	SCV002035107	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000194672	SCV002035194	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000194672	SCV002037468	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000512885	SCV002037870	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003917574	SCV004734147	likely benign	SPG11-related disorder	2019-09-23	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).