Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000272629 | SCV005061700 | uncertain significance | Glanzmann thrombasthenia | 2024-02-20 | reviewed by expert panel | curation | The c.1394-14C>T variant in ITGA2B is an intronic variant located within intron 13 of ITGA2B. It has been reported in ClinVar as part of a predisposition screen in an ostensibly healthy population. Thec.1394-14C>T variant is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of 0.023 (BP7). The highest population minor allele frequency in gnomAD v4.0.0 is 0.0004941 (45/91078 alleles) in the South Asian population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting. After a thorough literature search, this variant was not found to be reported in any published papers containing individuals with Glanzmann thrombasthenia. In summary, this variant meets the criteria to be classified as a VUS due to insufficient evidence for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BP7. (VCEP specifications version 2; date of approval 02/20/2024) |
| Illumina Laboratory Services, |
RCV000272629 | SCV000403378 | uncertain significance | Glanzmann thrombasthenia | 2018-01-13 | 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. |
| Labcorp Genetics |
RCV000272629 | SCV003482416 | likely benign | Glanzmann thrombasthenia | 2023-08-20 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488539 | SCV004241364 | likely benign | not specified | 2023-12-20 | criteria provided, single submitter | clinical testing | Variant summary: ITGA2B c.1394-14C>T alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00029 in 251438 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1394-14C>T in individuals affected with ITGA2B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |