Submissions for variant NM_000173.7(GP1BA):c.256C>T (p.Leu86Phe)

gnomAD frequency: 0.00007  dbSNP: rs13306411

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000502024	SCV000595019	likely benign	not specified	2017-06-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000502024	SCV004122437	benign	not specified	2023-10-31	criteria provided, single submitter	clinical testing	Variant summary: GP1BA c.256C>T (p.Leu86Phe) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 249204 control chromosomes, predominantly at a frequency of 0.0033 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 6-fold of the estimated maximal expected allele frequency for a pathogenic variant in GP1BA causing Bernard Soulier Syndrome phenotype (0.00059). Moreover, the variant has been reported at a frequency of 0.040 including 93 homozygotes in the ToMMo 54KJPN dataset of Japanese control individuals. These data strongly suggest that the variant is a benign polymorphism found primarily in populations of East Asian origin, and more specifically, in individuals of Japanese ancestry. To our knowledge, no occurrence of c.256C>T in individuals affected with Bernard Soulier Syndrome have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV003942583	SCV004762246	likely benign	GP1BA-related condition	2023-12-21	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477769	SCV000536894	uncertain significance	Bernard Soulier syndrome; Bernard-Soulier syndrome, type A2, autosomal dominant; Nonarteritic anterior ischemic optic neuropathy, susceptibility to; Pseudo von Willebrand disease	2015-12-18	no assertion criteria provided	research