Submissions for variant NM_013314.4(BLNK):c.88G>C (p.Gly30Arg)

gnomAD frequency: 0.00077  dbSNP: rs143109144

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000648341	SCV000770157	uncertain significance	Agammaglobulinemia 4, autosomal recessive	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 30 of the BLNK protein (p.Gly30Arg). This variant is present in population databases (rs143109144, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with BLNK-related conditions. ClinVar contains an entry for this variant (Variation ID: 538834). 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 expected to disrupt BLNK protein function. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001508300	SCV001714357	uncertain significance	not provided	2019-12-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001508300	SCV005093493	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing