Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ISTH- |
RCV000023565 | SCV002500872 | pathogenic | Bernard-Soulier syndrome, type A2, autosomal dominant | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV002512752 | SCV003443701 | pathogenic | not provided | 2023-07-25 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects GP1BA function (PMID: 1694864, 7690774, 11222377, 19067792). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GP1BA protein function. ClinVar contains an entry for this variant (Variation ID: 4156). This variant is also known as Bolzano mutation, Ala156Val. This missense change has been observed in individuals with the classical form of autosomal recessive Bernard-Soulier syndrome. It has also been reported in a heterozygous state with autosomal dominant macrothrombocytopenia in many families and has been considered as the most frequent cause of inherited thrombocytopenia in Italy (PMID: 7690774, 10235425, 11222377, 19067792, 21933849). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 172 of the GP1BA protein (p.Ala172Val). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000023565 | SCV004020487 | pathogenic | Bernard-Soulier syndrome, type A2, autosomal dominant | 2023-06-19 | criteria provided, single submitter | clinical testing | Variant summary: GP1BA c.515C>T (p.Ala172Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249014 control chromosomes (gnomAD). c.515C>T has been reported in the literature in numerous heterozygous individuals affected with Bernard-Soulier Syndrome, Type A2, Autosomal Dominant, and the variant has been shown to segregate with disease in related individuals (e.g., Savoia_2001, Noris_2012). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 21933849, 11222377). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000004373 | SCV000024544 | pathogenic | Bernard-Soulier syndrome, type A1 | 2001-03-01 | no assertion criteria provided | literature only | |
| OMIM | RCV000023565 | SCV000044856 | pathogenic | Bernard-Soulier syndrome, type A2, autosomal dominant | 2001-03-01 | no assertion criteria provided | literature only |