Submissions for variant NM_006612.6(KIF1C):c.1166-2A>T

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	RCV004783675	SCV005394782	likely pathogenic	Spastic ataxia 2	2024-09-24	criteria provided, single submitter	clinical testing	Variant summary: KIF1C c.1166-2A>T 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 KIF1C function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3' acceptor site. Three predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 247962 control chromosomes. To our knowledge, no occurrence of c.1166-2A>T in individuals affected with Spastic Ataxia 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.