Submissions for variant NM_000552.5(VWF):c.5170+1G>A

dbSNP: rs764543553

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003399191	SCV004122052	likely pathogenic	Hereditary von Willebrand disease	2023-10-24	criteria provided, single submitter	clinical testing	Variant summary: VWF c.5170+1G>A 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. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251478 control chromosomes. To our knowledge, no occurrence of c.5170+1G>A in individuals affected with Von Willebrand Disease 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 pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	RCV001787178	SCV001572705	likely pathogenic	von Willebrand disease type 3	2020-11-01	no assertion criteria provided	clinical testing	ClinGen Pathogenicity Calculator