Abstract Number: PB0621
Meeting: ISTH 2020 Congress
Background: Genetic analysis is important in the diagnosis of haemostatic disorders, and meaningful interpretation of results is an essential part of this process.
Aims: UK NEQAS distributes cases, providing a clinical scenario either with genetic analysis results, or with a blood sample for analysis. Laboratories produce an interpretation of the genetic variant detected in an informative report.
Methods: We describe here cases in which variable interpretation of genetic variants leads to different recommendations on submitted reports.
Results:
Case 1: Patient with DVT after knee arthroscopy, with a family history of thromboembolism. Borderline antithrombin activity was noted. Sequence analysis of SERPINC1 revealed heterozygosity for c.1246G>T. There was no overall consensus in reports on this variant (‘Antithrombin Cambridge’), with some centres reporting the variant as causative of disease phenotype, others as a variant of uncertain significance. Half of reports contained no comments regarding the ‘low’ thrombotic risk associated with this variant.
Case 2: Patient with FVII deficiency, and history of epistaxis and easy bruising. Genetic analysis of F7 revealed: c.1072A>T heterozygous; c.1285G>A heterozygous; c.1238G>A heterozygous. There was broad consensus when classifying the 3 variants; the majority of laboratories reporting both apparently compound heterozygous c.1072A>T and c.1285G>A variants (11/14 and 9/14 respectively) as causative of the disease phenotype and the c.1238G>A variant as a disease-associated polymorphism (DAP). However, in some reports increased importance was given to the DAP.
Case 3: Patient with severe haemophilia A, hemizygous for the F8 intron 22 inversion, whose mother did not carry the causative variant. There was broad consensus that mother may be a germline mosaic for the variant, however several laboratories did not acknowledge this possibility, resulting in production of potentially damaging reports.
Conclusions: A lack of consensus in interpretation for some of these cases underlines a need for EQA, supporting standardisation of both genetic laboratory testing and interpretation.
To cite this abstract in AMA style:
Jennings I, Hill M, Sutherland M, Millar C, Page A, Wheeler R, Walker I, Kitchen S, Goodeve A. Genetic Analysis for Investigation of Heritable Bleeding and Thrombotic Disorders – Variable Interpretation of Data Identified by the UK National External Quality Assessment Scheme (UK NEQAS) Blood Coagulation Programme [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/genetic-analysis-for-investigation-of-heritable-bleeding-and-thrombotic-disorders-variable-interpretation-of-data-identified-by-the-uk-national-external-quality-assessment-scheme-uk-neqas-blood-co/. Accessed March 21, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/genetic-analysis-for-investigation-of-heritable-bleeding-and-thrombotic-disorders-variable-interpretation-of-data-identified-by-the-uk-national-external-quality-assessment-scheme-uk-neqas-blood-co/