Submissions for variant NM_000419.5(ITGA2B):c.2930del (p.Arg977fs)

dbSNP: rs2048523431

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001225248	SCV001397500	pathogenic	Glanzmann thrombasthenia	2020-09-06	reviewed by expert panel	curation	The c.2930del variant has been reported in one compound heterozygous individual with phenotypes highly consistent with GT (PMID: 12083483). This frameshift variant occurs in exon 28 results in 63 altered amino acids followed by as stop loss and the elongation of the protein by 90 amino acids. The variant is absent from population databases including gnomAD, ExAC, and 1000 Genomes. In summary, this variant meets criteria to be classified as Likely Pathogenic for GT. GT-specific criteria applied: PVS1_Strong, PM2_Supporting, PM3, and PP4_Moderate.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001225248	SCV004298229	likely pathogenic	Glanzmann thrombasthenia	2023-11-04	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the ITGA2B gene (p.Arg977Glnfs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 63 amino acid(s) of the ITGA2B protein and extend the protein. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with Glanzmann thrombasthenia (PMID: 12083483, 20819594). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 953016). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.