ClinVar Miner

Submissions for variant NM_080680.3(COL11A2):c.2682G>A (p.Pro894=)

gnomAD frequency: 0.00068  dbSNP: rs113067047
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155071 SCV000204755 uncertain significance not specified 2016-07-21 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro894Pro var iant in COL11A2 has been previously reported by our laboratory in the heterozygo us state in 1 individual with hearing loss who also had several additional varia nts in other genes related to hearing loss. This variant has been identified in 0.2% (14/9576) of African chromosomes and 12/65002 European Chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs11306 7047). Although this variant has been seen in the general population, its freque ncy is not high enough to rule out a pathogenic role. This variant does not alte r the amino acid sequence, but is located in the last base of the exon, which is part of the 5' splice region. Computational tools do not suggest an impact to s plicing. However, this information is not predictive enough to rule out pathogen icity. In summary, while the clinical significance of the p.Pro894Pro variant is uncertain, these data suggest it is more likely to be benign.
GeneDx RCV001697115 SCV000717374 likely benign not provided 2021-08-12 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001154198 SCV001315533 uncertain significance Otospondylomegaepiphyseal dysplasia, autosomal recessive 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV001154199 SCV001315535 uncertain significance Otospondylomegaepiphyseal dysplasia, autosomal dominant 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV001154200 SCV001315536 uncertain significance Fibrochondrogenesis 2 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001697115 SCV002295904 uncertain significance not provided 2022-10-26 criteria provided, single submitter clinical testing This sequence change affects codon 894 of the COL11A2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL11A2 protein. This variant also falls at the last nucleotide of exon 36, which is part of the consensus splice site for this exon. This variant is present in population databases (rs113067047, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with COL11A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 178327). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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