Submissions for variant NM_000173.7(GP1BA):c.344T>C (p.Leu115Pro)

dbSNP: rs1597638598

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000851640	SCV000899680	likely pathogenic	Thrombocytopenia	2021-02-01	criteria provided, single submitter	research	We identified the heterozygous GP1BA variant (NM_000173.5:c.344T>C, NP_000164.5:p.Leu115Pro) in a female individual affected with familial thrombocytopenia, and classified it as a VUS. Co-segregation analysis has now been performed which allows us to reclassify the variant as likely pathogenic. We have now tested the 4 siblings in this family, 2 of whom are affected and have the variant and 2 who are unaffected and do not have the variant. An affected cousin of theirs was tested at Cambridge, UK (by Sanger) and they are also heterozygous for this variant. Using the algorithm suggested by Jarvik and Browning (Am Jour Hum Gen 98, 1077-1081, June 2, 2016) we have calculated that probability of this variant co-segregating with disease and not being pathogenic as 0.016, and so have increased the strength of this evidence (PP1) to strong. This, along with PM2 and PP3, means that we can now classify this variant as "likely pathogenic".
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002222624	SCV002500878	pathogenic	Bernard-Soulier syndrome, type A2, autosomal dominant		criteria provided, single submitter	clinical testing