Submissions for variant NM_015046.7(SETX):c.472T>G (p.Leu158Val)

gnomAD frequency: 0.00347  dbSNP: rs145438764

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000350037	SCV000477889	likely benign	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000399144	SCV000477890	benign	Amyotrophic lateral sclerosis type 4	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000513524	SCV000565556	likely benign	not provided	2021-04-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25174650, 25382069, 27013921, 29525178)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000513524	SCV000605100	likely benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513524	SCV000609358	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	SETX: BS1
Athena Diagnostics Inc	RCV000513524	SCV000615191	benign	not provided	2018-11-30	criteria provided, single submitter	clinical testing
Invitae	RCV001080659	SCV000645266	likely benign	Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2024-01-29	criteria provided, single submitter	clinical testing
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000350037	SCV001984420	likely benign	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2021-02-25	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848728	SCV002105160	likely benign	Hereditary spastic paraplegia	2021-09-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002338960	SCV002639104	likely benign	Inborn genetic diseases	2019-08-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003317200	SCV004021114	likely benign	not specified	2023-06-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003912567	SCV004733311	likely benign	SETX-related condition	2022-02-07	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).