Submissions for variant NM_000548.5(TSC2):c.5161-10A>C

gnomAD frequency: 0.30182  dbSNP: rs1800718

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000118712	SCV000205289	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	5161-10A>C in intron 40 of TSC2: This variant is not expected to have clinical s ignificance because it has been identified in 45.7% (2010/4396) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs1800718).
PreventionGenetics, part of Exact Sciences	RCV000118712	SCV000305240	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000042691	SCV000395676	benign	Tuberous sclerosis syndrome	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589236	SCV000605463	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000576820	SCV000677555	benign	Tuberous sclerosis 2	2017-04-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589236	SCV000697474	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The TSC2 c.5161-10A>C variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 24902/120464 (3635 homozygotes, 1/4), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic TSC2 variant of 1/14534 (0.0000688), suggesting this variant is likely a benign polymorphism. In addition, multiple reputable clinical laboratories cite the variant as "benign/likely benign." Therefore, the variant of interest has been classified as Benign.
Invitae	RCV000576820	SCV001717662	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000589236	SCV001940397	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000576820	SCV002039918	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002490592	SCV002804232	likely benign	Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2	2022-04-29	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000576820	SCV004016094	benign	Tuberous sclerosis 2	2023-07-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000576820	SCV004360941	benign	Tuberous sclerosis 2	2019-03-28	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000118712	SCV005087841	benign	not specified	2024-07-15	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 33% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 31. Only high quality variants are reported.
Tuberous sclerosis database (TSC2)	RCV000042691	SCV000066486	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Genetic Services Laboratory, University of Chicago	RCV000118712	SCV000153127	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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000118712	SCV001742344	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000118712	SCV001930016	benign	not specified		no assertion criteria provided	clinical testing