Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230887 | SCV003928827 | uncertain significance | not specified | 2023-04-24 | criteria provided, single submitter | clinical testing | Variant summary: GP9 c.284A>G (p.Tyr95Cys) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Cysteine-rich flanking region, C-terminal (IPR000483) of the encoded protein sequence. Another missense variant affecting this residue has been found in association with disease (HGMD). Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 244960 control chromosomes (gnomAD). c.284A>G has been reported in the literature in an individual affected with Bernard Soulier Syndrome (Savoia_2011). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Institute for Clinical Chemistry and Laboratory Medicine, |
RCV003329136 | SCV004031420 | pathogenic | Bernard Soulier syndrome | 2023-09-04 | criteria provided, single submitter | clinical testing | We identified this missense variant (284A>G) in one affected indiviudal of an Iranian family (PMID: 32202057; wrongly named 284G>A) which was diagnosed as having Bernard-Soulier syndrome (BSS) by Shahverdi et al (PMID: 29043243) (giant platelets, thrombocytopenia, bleeding phenotype, impaired platelet aggregation with ristocetin). The index case (daughter) was homozygous for GP9 c.284A>G, her asymptomatic parents heterozygous. She also presented with prekallikrein deficiency due to a larger deletion in KLKB1. GP9 c.284A>G can be found in dbSNP with a MAF <0.01% (rs1946583076) and prediction tools predict pathogenicity. GP9 is known to cause BSS and this exact variant was also identified as the cause of BSS in homozygosity in an unrelated case by Savoia et al (PMID: 21173099). Therfore, we classified this variant as pathogenic. |