ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3883+8C>G (rs45517316)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118704 SCV000169141 benign not specified 2013-01-14 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.
Invitae RCV001079257 SCV000261644 benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000118704 SCV000305205 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000043293 SCV000395635 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.
Athena Diagnostics Inc RCV000713930 SCV000844577 benign not provided 2018-01-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000118704 SCV000918331 benign not specified 2018-06-05 criteria provided, single submitter clinical testing Variant summary: TSC2 c.3883+8C>G alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 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 0.0039 in 274946 control chromosomes in the gnomAD database, including 24 homozygotes. The observed variant frequency is approximately 57-folds higher than 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.3883+8C>G in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Tuberous sclerosis database (TSC2) RCV000043293 SCV000067099 not provided Tuberous sclerosis syndrome no assertion provided curation
Genetic Services Laboratory, University of Chicago RCV000118704 SCV000153119 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.

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