Submissions for variant NC_000012.11:g.(?_6058042)_(6233837_?)del

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	RCV004782060	SCV005395208	pathogenic	von Willebrand disorder	2024-09-23	criteria provided, single submitter	clinical testing	Variant summary: The variant involves the deletion of exons 1-52 in the VWF gene. A presumed nomenclature of c.(?_-251)_(*139_?)del has been designated for the purposes of this classification. This deletion includes the entire coding sequence of the gene. As the exact proximal and distal breakpoints are unknown, it may extend beyond the annotated region of the gene to include other flanking genes. The variant allele was found at a frequency of 8.3e-06 in 120780 control chromosomes in the gnomAD database (Structural Variants v4.1 dataset). Whole VWF gene deletions have been reported in the literature in individuals affected with Von Willebrand Disease (e.g. Yadegari_2012, Veyradier_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 22871923, 26986123). ClinVar contains entries for large deletion variants that cover the entire VWF gene (e.g. Variation IDs: 1527679, 1065230). Based on the evidence outlined above, the variant was classified as pathogenic.