ClinVar Miner

Submissions for variant NM_000212.3(ITGB3):c.55del (p.Ala19fs)

dbSNP: rs1302506624
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV004577558 SCV005061663 uncertain significance Glanzmann thrombasthenia 2024-02-20 reviewed by expert panel curation The c.55del variant in ITGB3 is a deletion of 1 nucleotide in exon 1, resulting in a shift of the reading frame and a premature stop signal (p.Ala19Argfs*7). Premature termination codon within exon 1/ first 100 nucleotides may not cause NMD and instead may lead to translation re-initiation (PMID: 27618451). Therefore, PVS1 is downgraded to PVS1_moderate. This variant occurs at a very low allele frequency overall in gnomAD v4.0.0 of 0.000006374 with a MAF of 0.000002980 (3/1006570) in the non-Finnish European population (PM2_Supporting). The variant has been reported heterozygous in one individual (PMID: 31980526) but has not been reported in any patients with a Glanzmann thrombasthenia phenotype. In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_Moderate, PM2_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001948884 SCV002213175 pathogenic not provided 2023-05-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1438062). This variant has not been reported in the literature in individuals affected with ITGB3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ala19Argfs*7) in the ITGB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ITGB3 are known to be pathogenic (PMID: 21917754).

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