Submissions for variant NM_004937.3(CTNS):c.970+15G>A

gnomAD frequency: 0.03340  dbSNP: rs76153698

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000251725	SCV000305962	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000346193	SCV000402243	benign	Ocular cystinosis	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	RCV000392247	SCV000402244	benign	Nephropathic cystinosis	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590580	SCV000698528	benign	not provided	2017-06-05	criteria provided, single submitter	clinical testing	Variant summary: The CTNS c.970+15G>A variant involves the alteration of a non-conserved intronic nucleotide at a position not widely known to affect gene splicing. Mutation taster predicts a benign outcome for this variant. This variant was found in 2496/120078 control chromosomes (45 homozygotes) from ExAC at a frequency of 0.0207865, which is approximately 8 times the estimated maximal expected allele frequency of a pathogenic CTNS variant (0.0025), suggesting this variant is likely a benign polymorphism. It is more common in African subpopulation with an allele frequency of 6.5% (674/10238 chromosomes). This variant was found in a cystinosis patient who carried c.140+1G>T in homozygous state, further supporting benign outcome of the variant of interest. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002518597	SCV001720837	benign	Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000590580	SCV001911975	benign	not provided	2018-12-31	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590580	SCV005252210	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000590580	SCV000801410	benign	not provided	2016-02-03	no assertion criteria provided	clinical testing