Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000153086 | SCV000202542 | uncertain significance | not provided | 2017-10-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000704454 | SCV000833404 | likely benign | Bethlem myopathy 1A | 2025-01-07 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000153086 | SCV003832576 | uncertain significance | not provided | 2022-09-02 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700477 | SCV005204192 | uncertain significance | not specified | 2024-06-20 | criteria provided, single submitter | clinical testing | Variant summary: COL6A2 c.2528G>A (p.Arg843Gln) results in a conservative amino acid change located in the von Willebrand factor, type A domain (IPR002035) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 239254 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in COL6A2 causing Collagen Type VI-Related Disorders, allowing no conclusion about variant significance. c.2528G>A has been reported in the literature in the heterozygous state in an individual affected with Bethlem myopathy (Foley_2013), in a compound heterozygous individual with a suspected muscle disorder who underwent multigene panel testing and also had compound heterozygous variants in the CAPN3 gene (Thuriot_2020), and in an individual affected with Down syndrome who had atrioventricular septal defect (Ackerman_2012). These reports do not provide unequivocal conclusions about association of the variant with Collagen Type VI-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23040494, 24271325, 32337335). ClinVar contains an entry for this variant (Variation ID: 166934). Based on the evidence outlined above, the variant was classified as uncertain significance. |