- Nov 2024
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Disease: Platelet-type Von-willebrand Disorder (PT-VWD)
Patient: 17 yo, male, adopted
Variant: GP1BA NM_000173.7: c:580C>T p.(P.Leu194Phe), Heterozygous, gain-of-function
Phenotypes: moderate bleeding phenotype, ISTH-BAT bleeding score of 3, recurrent epistaxis, easy bruising, mild thrombocytopenia
Family: Adopted, no other family history mentioned, segregation studies not performed.
Genetic analysis performed: found variant in GP1BA, results obtained by sanger sequencing.
Variant present in gnomAD(rs368111193): low allele frequency, contradictory classifications
Variant is not present in ClinVar, LOVD, or HGMD databases
According to this paper, ACMG guidelines classified this variant as a VUS.
This paper entered it into Clinvar (var ID 1693270)
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- Oct 2024
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journals.lww.com journals.lww.com
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Disease: mild haemophilia A, influencing VWF levels
Patient: 20 yo, Female
Variant1: F8 NM_000132.3: c.1127T>G: p. Val376Gly (Exon 8, current clinvar interpretation not available)
Variant 2: F8 NM_000132.3: c.3780C>G: p. Asp1260Glu (Exon 14, current ClinVar interpretation is benign)
Variant 3: VWF NM_000552.5: c.1415A>G:p.His484Arg (Exon 13, current ClinVar interpretation is Benign/likely Benign)
Variant 4: VWF NM_000552.5: c.2365A>G:p.Thr789Ala (Exon 18, current ClinVar interpretation is Benign/ likely Benign)
Variant 5: VWF NM_000552.5: c.2771G>A:p.Arg924Gln (Exon 21, current ClinVar interpretation is conflicting interpretations of pathogenicity (VUS-3)(Benign-4)(Likely benign-1))
Variant 6: VWF NM_000552.5: c.4141A>G:p.Thr1381Ala (Exon 28, current ClinVar interpretation is Benign/ Likely Benign)
Variant 7: VWF NM_000552.5: c.6532G>T:p.Ala2178Ser (Exon 37, Conflicting interpretations of pathogenicity: (VUS-1) (Likely Benign-1))
Variant 8: F5 NM_000130.5: c.2773A>G:p.Lys925Glu (Exon 13, current ClinVar interpretation is Benign/Likely Benign)
Variant 9: F5 NM_000130.5: c.2594A>G:p.His865Arg (Exon 13, current ClinVar interpretation is Benign/Likely Benign)
Variant 10: F5 NM_000130.5: c.2573A>G:p.Lys858Arg (Exon 13, Conflicting interpretations of pathogenicity: (VUS-1) (Benign-2)(Likely Benign-1))
Variant 11: F5 NM_000130.5: c.5290A>G:p.Met1764Val (Exon 16, Conflicting interpretations of pathogenicity: (VUS-1) (Benign-2)(Likely Benign-1))
Variant 12: F13A1 NM_000129.4: c.103G>T:p.Val35Leu (Exon 2, Conflicting interpretations of pathogenicity: (VUS-1) (Benign-3))
Variant notes: All are heterozygous
Both variants in F8 are linked to reports associated with haemophilia, though second variant is considered benign.
Phenotypes: History of bleeding (Heavy mentrual bleeding since menarche)(Treated with transdermal oestrogen and Levonorgestel), iron deficiency anaemia. High Janssen score for pictorial blood assessment. Gum bleeding lasting longer than 10 minutes(Treated with local application of tranexamic acid), recurrent nosebleeds, high score for ISTH and BAT assessments. Decrease in VWF:Ag ratio, VWF:CB ratio decreased, VWF: GPIbR ratio decreased
Family: Maternal grandfather possibly haemophiliac, mother asymptomatic
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