Submissions for variant NM_000548.5(TSC2):c.5068+9G>A

gnomAD frequency: 0.00026  dbSNP: rs45445593

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724754	SCV000229938	uncertain significance	not provided	2015-04-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079713	SCV000285438	benign	Tuberous sclerosis 2	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000724754	SCV000515057	likely benign	not provided	2018-04-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000177971	SCV000918333	benign	not specified	2018-10-01	criteria provided, single submitter	clinical testing	Variant summary: TSC2 c.5068+9G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00016 in 276130 control chromosomes (gnomAD). The observed variant frequency is approximately 2.26 fold of the estimated maximal expected allele frequency for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex phenotype (6.9e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.5068+9G>A in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as benign.
Athena Diagnostics	RCV000177971	SCV005622659	benign	not specified	2024-09-16	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042702	SCV000066497	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Clinical Genetics, Academic Medical Center	RCV000724754	SCV001920384	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000177971	SCV001964807	benign	not specified		no assertion criteria provided	clinical testing