ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.6511+5G>A (rs200608284)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000179087 SCV000168507 benign not specified 2014-03-15 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000179087 SCV000231281 benign not specified 2014-09-05 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000179087 SCV000308632 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000242451 SCV000318325 benign Cardiovascular phenotype 2015-06-04 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Clinical Services Laboratory,Illumina RCV000363479 SCV000452568 benign Congenital contractural arachnodactyly 2018-01-12 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.
Invitae RCV000363479 SCV000563048 benign Congenital contractural arachnodactyly 2019-12-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589750 SCV000697898 benign not provided 2017-03-22 criteria provided, single submitter clinical testing Variant summary: The FBN2 c.6511+5G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing and ESE Finder predicts no significant effect on ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in ExAC at a frequency of 0.0049729 (549/110398 control chromosomes [2 homozygotes]), which is approximately 3978 times the estimated maximal expected allele frequency of a pathogenic FBN2 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768219 SCV000898703 uncertain significance Congenital contractural arachnodactyly; Macular degeneration, early-onset 2017-09-21 criteria provided, single submitter clinical testing FBN2 NM_001999.3 exon 51 c.6511+5G>A: This variant has not been reported in the literature but is present in 0.7% (894/125710) of European individuals including 3 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs200608284). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign (Variation ID:137344). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282129 SCV001156686 benign none provided 2020-05-15 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000589750 SCV001800440 likely benign not provided no assertion criteria provided clinical testing

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