ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5068+9G>A (rs45445593)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724754 SCV000229938 uncertain significance not provided 2015-04-16 criteria provided, single submitter clinical testing
Invitae RCV000231552 SCV000285438 benign Tuberous sclerosis 2 2017-12-22 criteria provided, single submitter clinical testing
GeneDx RCV000177971 SCV000515057 likely benign not specified 2017-09-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America 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.
Tuberous sclerosis database (TSC2) RCV000042702 SCV000066497 not provided Tuberous sclerosis syndrome no assertion provided curation

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