Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000778501 | SCV001397507 | likely pathogenic | Glanzmann thrombasthenia | 2023-08-15 | reviewed by expert panel | curation | The NM_000212.3(ITGB3):c.362-1G>A splice variant alters the acceptor site of intron 3 and is expected to result in the out of frame skipping of exon 4, the resulting frameshift would generate a stop codon in the next position and is predicted to cause NMD (PVS1). This variant has not been reported in the literature, to our knowledge and has only been observed by Illumina in a predisposition screen in an ostensibly healthy population. It is absent from gnomADv2.1.1 (PM2_supporting). In summary, this variant meets the criteria to be classified likely pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_Supporting, PVS1 (PD VCEP specifications version 2.1). |
Illumina Laboratory Services, |
RCV000778501 | SCV000914772 | uncertain significance | Glanzmann thrombasthenia | 2018-10-15 | criteria provided, single submitter | clinical testing | This variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Due to the potential impact of splice acceptor variants and the lack of clarifying evidence, this variant is classified as a variant of uncertain significance but suspicious for pathogenicity for this disease. |