ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.2566-6A>G

gnomAD frequency: 0.00012  dbSNP: rs141088934
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005238949 SCV005883355 uncertain significance not specified 2024-12-17 criteria provided, single submitter clinical testing Variant summary: COL1A2 c.2566-6A>G 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. Consensus agreement among computation 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 0.0004 in 1613224 control chromosomes, predominantly at a frequency of 0.00053 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in COL1A2 causing Osteoporosis (0.0004 vs 0.0014), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2566-6A>G in individuals affected with Osteoporosis and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 360964). Based on the evidence outlined above, the variant was classified as uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001697767 SCV005876643 likely benign not provided 2024-03-04 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002278616 SCV002565570 uncertain significance Ehlers-Danlos syndrome 2022-06-02 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001697767 SCV002062760 uncertain significance not provided 2021-10-01 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000680489 SCV000807867 likely benign Connective tissue disorder 2018-06-01 criteria provided, single submitter clinical testing
GeneDx RCV001697767 SCV000717464 likely benign not provided 2021-04-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002229989 SCV000627316 likely benign Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2025-01-13 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000299556 SCV000470612 likely benign Osteogenesis imperfecta 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV000263221 SCV000470611 benign Ehlers-Danlos syndrome, arthrochalasia type, 2 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.

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