TY - JOUR
T1 - GoldVariants, a resource for sharing rare genetic variants detected in bleeding, thrombotic and platelet disorders
T2 - communication from the ISTH SSC Subcommittee on Genomics in Thrombosis and Hemostasis
AU - Megy, Karyn
AU - Downes, Kate
AU - Morel‐kopp, Marie‐christine
AU - Bastida, José M
AU - Brooks, Shannon
AU - Bury, Loredana
AU - Leinoe, Eva
AU - Gomez, Keith
AU - Morgan, Neil V
AU - Othman, Maha
AU - Ouwehand, Willem H
AU - Perez Botero, Juliana
AU - Rivera, José
AU - Schulze, Harald
AU - Trégouët, David‐alexandre
AU - Freson, Kathleen
PY - 2021/7/13
Y1 - 2021/7/13
N2 - The implementation of High Throughput Sequencing (HTS) technologies in research and diagnostic laboratories has linked many new genes to rare bleeding, thrombotic and platelet disorders (BTPD), and revealed multiple genetic variants linked to those disorders, many of them being of uncertain pathogenicity when considering the accepted evidences (variant consequence, frequency in control datasets, number of reported patients, prediction models, and functional assays). The sequencing effort has also resulted in resources for gathering disease-causing variants associated with specific genes, but for BTPD, such well-curated databases exist only for a few genes. On the other hand, submissions by individuals or diagnostic laboratories to the variant database ClinVar are hampered by the lack of a submission process tailored to capture the specific features of haemostatic diseases. As we move toward the implementation of HTS in the diagnosis of BTPD, the Scientific and Standardization Committee for Genetics in Thrombosis and Haemostasis has developed and tested a REDCap-based interface, aimed at the community, to submit curated genetic variants for diagnostic-grade BTPD genes. Here, we describe the use of the interface and the initial submission of 821 variants from 30 different centers covering 14 countries. This open-access variant resource will be shared with the community to improve variant classification and regular bulk data transfer to ClinVar.
AB - The implementation of High Throughput Sequencing (HTS) technologies in research and diagnostic laboratories has linked many new genes to rare bleeding, thrombotic and platelet disorders (BTPD), and revealed multiple genetic variants linked to those disorders, many of them being of uncertain pathogenicity when considering the accepted evidences (variant consequence, frequency in control datasets, number of reported patients, prediction models, and functional assays). The sequencing effort has also resulted in resources for gathering disease-causing variants associated with specific genes, but for BTPD, such well-curated databases exist only for a few genes. On the other hand, submissions by individuals or diagnostic laboratories to the variant database ClinVar are hampered by the lack of a submission process tailored to capture the specific features of haemostatic diseases. As we move toward the implementation of HTS in the diagnosis of BTPD, the Scientific and Standardization Committee for Genetics in Thrombosis and Haemostasis has developed and tested a REDCap-based interface, aimed at the community, to submit curated genetic variants for diagnostic-grade BTPD genes. Here, we describe the use of the interface and the initial submission of 821 variants from 30 different centers covering 14 countries. This open-access variant resource will be shared with the community to improve variant classification and regular bulk data transfer to ClinVar.
KW - Blood
KW - genes
KW - hemorrhage
KW - mutation
KW - platelets
KW - thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85111866177&partnerID=8YFLogxK
U2 - 10.1111/jth.15459
DO - 10.1111/jth.15459
M3 - Article
SN - 1538-7933
VL - 19
SP - 2612
EP - 2617
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 10
ER -