Submissions for variant NM_014363.6(SACS):c.7528G>A (p.Ala2510Thr)

gnomAD frequency: 0.00131  dbSNP: rs111920492

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003891946	SCV000312160	likely benign	SACS-related condition	2019-05-21	criteria provided, single submitter	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).
GeneDx	RCV000710207	SCV000576775	uncertain significance	not provided	2023-07-10	criteria provided, single submitter	clinical testing	Observed with two other SACS variants, phase unknown, in an individual with rigidity, bradykinesia, slow speech production, and abnormal brain MRI in the published literature (Wagner et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23280630, 35008978, 29379980)
Athena Diagnostics Inc	RCV000243536	SCV000614977	likely benign	not specified	2021-04-23	criteria provided, single submitter	clinical testing
Invitae	RCV001082626	SCV000629481	likely benign	Spastic paraplegia	2024-01-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001112102	SCV001269723	uncertain significance	Charlevoix-Saguenay spastic ataxia	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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000710207	SCV001713621	uncertain significance	not provided	2019-07-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001112102	SCV002026612	likely benign	Charlevoix-Saguenay spastic ataxia	2021-09-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848029	SCV002105084	uncertain significance	Hereditary spastic paraplegia	2021-07-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000710207	SCV004033239	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	SACS: BS2
Natera, Inc.	RCV001112102	SCV001460042	uncertain significance	Charlevoix-Saguenay spastic ataxia	2020-01-10	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000710207	SCV001744325	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000710207	SCV001968661	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000710207	SCV001979701	uncertain significance	not provided		no assertion criteria provided	clinical testing