Submissions for variant NM_003238.6(TGFB2):c.1086+2T>C

dbSNP: rs1660010402

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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.
GeneDx	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