Submissions for variant NM_014363.6(SACS):c.8853T>C (p.Val2951=)

gnomAD frequency: 0.21755  dbSNP: rs9552929

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000118234	SCV000225025	benign	not specified	2014-09-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000118234	SCV000312162	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000372801	SCV000383319	likely benign	Charlevoix-Saguenay spastic ataxia	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000118234	SCV000918181	benign	not specified	2017-10-19	criteria provided, single submitter	clinical testing	Variant summary: The SACS c.8853T>C (p.Val2951Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions have yet to be confirmed by functional studies. This variant was found in 74944/252514 control chromosomes (127 homozygotes) at a frequency of 0.2967915, which is approximately 38 times the estimated maximal expected allele frequency of a pathogenic SACS variant (0.0079057), suggesting this variant is likely a benign polymorphism. This variant has been reported in a validation study with high allele frequency and was classified as polymorphism by authors (Vermeer_2009). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Athena Diagnostics	RCV000118234	SCV001475444	benign	not specified	2019-09-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001517095	SCV001725509	benign	Spastic paraplegia	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000372801	SCV001750105	benign	Charlevoix-Saguenay spastic ataxia	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000676356	SCV001867079	benign	not provided	2018-07-31	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19779133)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847722	SCV002105108	benign	Hereditary spastic paraplegia	2016-12-12	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000676356	SCV005219345	likely benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000118234	SCV000152593	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Mayo Clinic Laboratories, Mayo Clinic	RCV000676356	SCV000802131	benign	not provided	2016-02-19	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000372801	SCV001459488	benign	Charlevoix-Saguenay spastic ataxia	2020-09-16	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000118234	SCV001952280	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118234	SCV001967804	benign	not specified		no assertion criteria provided	clinical testing