ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.1036-14G>A (rs114322680)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000441752 SCV000052240 benign not specified 2018-09-06 criteria provided, single submitter clinical testing Variant summary: COL1A2 c.1036-14G>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. 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 0.0011 in 277092 control chromosomes, predominantly at a frequency of 0.012 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 426.66 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL1A2 causing Osteogenesis Imperfecta phenotype (2.8e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1036-14G>A in individuals affected with Osteogenesis Imperfecta and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV000326210 SCV000470575 likely benign Osteogenesis Imperfecta, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000380485 SCV000470576 likely benign Ehlers-Danlos syndrome, procollagen proteinase deficient 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000441752 SCV000529306 benign not specified 2017-01-17 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000441752 SCV001159108 benign not specified 2018-09-19 criteria provided, single submitter clinical testing

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