Submissions for variant NM_015311.3(OBSL1):c.2134+2T>C

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	RCV004783361	SCV005395091	likely pathogenic	3M syndrome 2	2024-09-09	criteria provided, single submitter	clinical testing	Variant summary: OBSL1 c.2134+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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of OBSL1 function. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. One predict the variant no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 232006 control chromosomes. To our knowledge, no occurrence of c.2134+2T>C in individuals affected with Three M Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.