ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.3015G>A (p.Leu1005=) (rs28763946)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000117021 SCV000168482 benign not specified 2013-03-28 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000117021 SCV000269094 benign not specified 2013-04-04 criteria provided, single submitter clinical testing Leu1005Leu in exon 24 of FBN2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 2.9% (247/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs28763946).
PreventionGenetics,PreventionGenetics RCV000117021 SCV000308607 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000253849 SCV000317712 benign Cardiovascular phenotype 2014-12-12 criteria provided, single submitter clinical testing 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 RCV000385441 SCV000452617 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 RCV000385441 SCV000563042 benign Congenital contractural arachnodactyly 2020-12-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586504 SCV000697893 benign not provided 2017-03-29 criteria provided, single submitter clinical testing Variant summary: The FBN2 c.3015G>A (p.Leu1005Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1779/121186 control chromosomes (20 homozygotes) at a frequency of 0.0146799, which is approximately 11744 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. Taken together, this variant is classified as benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000385441 SCV000743982 benign Congenital contractural arachnodactyly 2014-10-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283390 SCV001156621 benign none provided 2020-08-27 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000117021 SCV000151143 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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000385441 SCV000745934 benign Congenital contractural arachnodactyly 2014-11-19 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000117021 SCV001798689 benign not specified no assertion criteria provided clinical testing

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