Submissions for variant NM_000089.4(COL1A2):c.739G>A (p.Gly247Ser)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479810	SCV004223618	likely pathogenic	Ehlers-Danlos syndrome	2023-11-02	criteria provided, single submitter	clinical testing	Variant summary: COL1A2 c.739G>A (p.Gly247Ser) results in a non-conservative amino acid change in the encoded protein sequence. The variant affects a Glycine residue of the triple-helical region containing Gly-X-Y repeats, which is a known disease mechanism for this gene. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251456 control chromosomes. 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.739G>A in individuals affected with Ehlers-Danlos Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. However, several other variants affecting the same codon have been reported in HGMD in patients with Osteogenesis imperfecta (p.G247R, p.G247D, p.G247V). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.