Submissions for variant NM_152490.5(B3GALNT2):c.439G>C (p.Val147Leu)

dbSNP: rs143983025

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000193251	SCV000246777	uncertain significance	not specified	2015-02-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000766719	SCV000583206	uncertain significance	not provided	2017-05-25	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the B3GALNT2 gene. The V147L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V147L variant is observed in 3/11566 (0.03%) alleles from individuals of Latino background, in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V147L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000651069	SCV000772918	uncertain significance	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11	2022-09-19	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 147 of the B3GALNT2 protein (p.Val147Leu). This variant is present in population databases (rs143983025, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with B3GALNT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 210513). 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 B3GALNT2 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.