Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174870 | SCV001338264 | likely pathogenic | Familial aortopathy | 2020-02-14 | criteria provided, single submitter | clinical testing | Variant summary: TGFB2 c.1086+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' canonical splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 244770 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1086+2T>C in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Gene |
RCV003156317 | SCV003845753 | likely pathogenic | not provided | 2022-09-22 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |