Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001125482 | SCV003916011 | uncertain significance | Glanzmann thrombasthenia | 2023-01-17 | reviewed by expert panel | curation | The variant NM_000212.3(ITGB3):c.1157G>A is a missense variant predicted to cause substitution of Arginine by Histidine at amino acid 386. This variant has not been found in any individuals with Glanzmann thrombasthenia after a thorough literature search. This variant is found at a very low rate of 0.000008790 (1/113764) within the European (non-Finnish) population in gnomAD (PM2_Supporting). The computational predictor REVEL gives a score of .25, which predicts no damaging effect on ITGB3 function. This variant was identified by Illumina and found in a screen of an ostensibly healthy population. In summary, this variant meets the criteria to be classified as Uncertain significance - insufficient evidence for autosomal recessive inheritance of Glanzmann thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_Supporting and BP4 (VCEP specifications version 2.1). |
Illumina Laboratory Services, |
RCV001125482 | SCV001284556 | uncertain significance | Glanzmann thrombasthenia | 2018-04-20 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory 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, this variant 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, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |