Submissions for variant NM_000552.5(VWF):c.5049A>C (p.Ala1683=)

gnomAD frequency: 0.01607  dbSNP: rs79275181

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000307103	SCV000332983	uncertain significance	not provided	2015-07-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000291213	SCV000380592	uncertain significance	Hereditary von Willebrand disease	2016-06-14	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820811	SCV002068268	uncertain significance	not specified	2020-08-17	criteria provided, single submitter	clinical testing
Mendelics	RCV001820811	SCV002516740	benign	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV004816481	SCV005439067	uncertain significance	von Willebrand disease type 2	2023-06-22	criteria provided, single submitter	clinical testing	The observed synonymous c.5049A>C p.Ala1683Ala variant in VWF gene has not been reported in affected individuals previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ala1683Ala variant is absent gnomAD Exomes. This variant has been submitted to ClinVar database as Benign / Uncertain Significance multiple submissions. The splice site is located 5 position downstream of this variant. As this synonymous variant lies in the splice region, functional studies are required to prove the pathogenicity. Hence, for these reasons, this variant is classified as Variant of Uncertain Significance VUS.
Neuberg Centre For Genomic Medicine, NCGM	RCV005055818	SCV005690611	uncertain significance	von Willebrand disease type 1	2023-06-22	criteria provided, single submitter	clinical testing	The synonymous c.5049A>C (p.Ala1683Ala) variant in VWF gene has not been reported in affected individuals previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ala1683Ala variant is absent gnomAD exomes database. This variant has been submitted to ClinVar database as Uncertain Significance/Likely Benign (multiple submissions). The splice site is located 5 position downstream of this variant. As this synonymous variant lies in the splice region, functional studies are required to prove the pathogenicity. Hence, for these reasons, this variant is classified as Variant of Uncertain Significance (VUS).