Submissions for variant NM_015046.7(SETX):c.7371T>C (p.His2457=)

gnomAD frequency: 0.00399  dbSNP: rs113071480

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000307888	SCV000477791	benign	Amyotrophic lateral sclerosis type 4	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 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.
Illumina Laboratory Services, Illumina	RCV000362769	SCV000477792	benign	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	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 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.
Invitae	RCV001083549	SCV000645288	benign	Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2024-01-21	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000556056	SCV001145579	benign	not provided	2019-02-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000556056	SCV001789001	likely benign	not provided	2021-01-30	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848724	SCV002105189	likely benign	Hereditary spastic paraplegia	2022-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002379257	SCV002672088	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: 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-Nilou Lab	RCV000362769	SCV003931766	likely benign	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000307888	SCV003931777	likely benign	Amyotrophic lateral sclerosis type 4	2023-02-08	criteria provided, single submitter	clinical testing