ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.2602-3C>G

gnomAD frequency: 0.00003  dbSNP: rs763330792
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV000003027 SCV001397514 likely pathogenic Glanzmann thrombasthenia 2023-09-07 reviewed by expert panel curation The NM_000419.4:c.2602-3C>G variant is a splice region variant that is predicted to result in abnormal splicing and is shown to skip exon 26 in RNA studies from a patient (PMID: 1317725), resulting in an in-frame deletion of Val868 to Val909 (3.9% of the protein; PM4). It occurs at a low frequency in gnomADv2.1.1 with a MAF of 0.00006523 in the East Asian population (PM2_supporting). At least 3 compound heterozygous probands are reported in the literature, with the other variants being Leu973AlafsTer63, Leu214Pro, and Ala777Asp (PMID: 15748238, PMID: 27696190, PMID: 29675921; PM3). In summary, based on the available evidence at this time, the c.2602-3C>G variant is classified as likely pathogenic. GT-specific criteria applied: PM2_supporting, PM3, PM4, PP4_strong.
Labcorp Genetics (formerly Invitae), Labcorp RCV000003027 SCV003441986 pathogenic Glanzmann thrombasthenia 2022-09-26 criteria provided, single submitter clinical testing Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 26, but is expected to preserve the integrity of the reading-frame (PMID: 1317725). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2893). This variant has been observed in individual(s) with Glanzmann thrombasthenia (PMID: 1317725, 29675921). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change falls in intron 25 of the ITGA2B gene. It does not directly change the encoded amino acid sequence of the ITGA2B protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product.
OMIM RCV001580164 SCV000023185 pathogenic Glanzmann thrombasthenia 1 1992-06-15 no assertion criteria provided literature only

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