ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.8351C>T (p.Pro2784Leu) (rs144574441)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000246954 SCV000308660 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000251391 SCV000320222 benign Cardiovascular phenotype 2015-08-30 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Illumina Clinical Services Laboratory,Illumina RCV000296777 SCV000452535 benign Congenital contractural arachnodactyly 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.
GeneDx RCV000246954 SCV000513027 benign not specified 2015-07-30 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 RCV000296777 SCV000563009 benign Congenital contractural arachnodactyly 2020-11-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589213 SCV000697906 benign not provided 2017-03-29 criteria provided, single submitter clinical testing Variant summary: The FBN2 c.8351C>T (p.Pro2784Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution. The variant does not lie within a known functional domain (InterPro) and 4/5 in silico tools predict a benign outcome for this variant. This variant was found in the large control database ExAC in 759 of 121388 control chromosomes (26 homozygotes), predominantly observed in the South Asian subpopulation at a frequency of 0.04524 (747/16512). This frequency is about 36192 times the estimated maximal expected allele frequency of a pathogenic FBN2 variant (0.0000013), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285184 SCV001471576 benign none provided 2019-12-20 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000589213 SCV001798690 likely benign not provided no assertion criteria provided clinical testing

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