Submissions for variant NM_000089.4(COL1A2):c.2674-6G>C

dbSNP: rs771442891

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002243120	SCV001614990	likely benign	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2022-11-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003490244	SCV004241313	uncertain significance	not specified	2023-12-19	criteria provided, single submitter	clinical testing	Variant summary: COL1A2 c.2674-6G>C 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 4e-06 in 251270 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2674-6G>C in individuals affected with Ehlers-Danlos Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.