Submissions for variant NM_000419.5(ITGA2B):c.1375G>A (p.Asp459Asn)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV003314537	SCV004014033	uncertain significance	Glanzmann thrombasthenia 1		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003427733	SCV004140680	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003777284	SCV004660192	uncertain significance	Glanzmann thrombasthenia	2023-08-03	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ITGA2B protein function. ClinVar contains an entry for this variant (Variation ID: 2572652). This variant has not been reported in the literature in individuals affected with ITGA2B-related conditions. This variant is present in population databases (rs181511536, gnomAD 0.009%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 459 of the ITGA2B protein (p.Asp459Asn).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526250	SCV005040447	uncertain significance	not specified	2024-03-04	criteria provided, single submitter	clinical testing	Variant summary: ITGA2B c.1375G>A (p.Asp459Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251478 control chromosomes. To our knowledge, no occurrence of c.1375G>A in individuals affected with ITGA2B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2572652). Based on the evidence outlined above, the variant was classified as uncertain significance.