Disease: Dystrophic epidermolysis bullosa (DEB) pruriginosa *Note: A novel vwf variant was found in this patient with these other variants in COL7A1 gene

Patient(s): 17 YO Korean male

Variant: VWF NM_000552.5: c.3310C>T p. (R1101W) Located in exon 26

Hadn't been reported previously Variant found to be inherited in trans from family analysis

According to the paper, they have classified with with ACMG guidelines as likely pathogenic.

Reasoning: Variant absent in the Korea Ref Genome Database and Allele Freq = 0.00086% in gnomAD (Evidence: PM2)

Variant detected in trans with another well-known pathologic variant (c.5797C>T) (Evidence: PM3)

Multiple missense variants are known to be pathogenic in RDEB (Evidence: PP2)

Various computational in silico predictive programs reported the variant as pathogenic (Evidence PP3)

Disease: Von-willebrand Disease (Type 2A)

Patient: 50 yo female

Variant: VWF NM_000552.5 c:4232_4249del p.(Val411_Ile416del), Exon 28, heterozygous variant

According to this paper, ACMG-AMP guidelines for interpreting this variant resulted in classification of likely pathogenic

Phenotypes: increased bruising, fatigue, recurrent sinusitis, menorrhagia, neutropenia, anaemia. Reduction in high-molecular-weight multimers

Family: segregation analysis showed two affected family members had the variant and two unaffected family members did not have variant.

Note: Patient also has diagnosed Acute Myeloid Leukaemia (AML) NM_000546.6(TP53):c704A>G p.(Asn235Ser), listed as VUS and found by NGS