Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| NIHR Bioresource Rare Diseases, |
RCV000852069 | SCV000899594 | pathogenic | Macrothrombocytopenia | 2019-02-01 | criteria provided, single submitter | research | |
| Labcorp Genetics |
RCV001204218 | SCV001375417 | pathogenic | not provided | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 71 of the GP9 protein (p.Phe71Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Bernard-Soulier Syndrome and/or Bernard-Soulier syndrome (PMID: 9163595, 21699652, 25539746, 28395735, 29636940). This variant is also known as Phe55Ser. ClinVar contains an entry for this variant (Variation ID: 13531). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Phe71 amino acid residue in GP9. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21699652; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| ISTH- |
RCV002222350 | SCV002500885 | pathogenic | Bernard Soulier syndrome | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222350 | SCV002547882 | pathogenic | Bernard Soulier syndrome | 2022-05-25 | criteria provided, single submitter | clinical testing | Variant summary: GP9 c.212T>C (p.Phe71Ser) results in a non-conservative amino acid change located in the Leucine-rich repeat (IPR001611) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248306 control chromosomes (gnomAD). c.212T>C has been reported in the literature in multiple homozygous individuals affected with Bernard Soulier Syndrome (Noris_1997, Suzuki_1997, Sumitha_2011, Sanchez-Guiu_2014, Savoia_2011). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported, however it is suggested that disruption of the the leucine-rich repeat motif impairs surface expression of the GPIb/IX/V complex (Sumitha_2011, Suzuki_1997). Other substitutions at this codon (Phe>Cys) have also been found to impact surface GPIb/IX/V expression (Sumitha_2011). Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and the other as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000014486 | SCV000034737 | pathogenic | Bernard-Soulier syndrome type C | 1997-05-01 | no assertion criteria provided | literature only |