ClinVar Miner

Submissions for variant NM_152490.5(B3GALNT2):c.439G>C (p.Val147Leu) (rs143983025)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Genetic Services Laboratory, University of Chicago RCV000193251 SCV000246777 uncertain significance not specified 2015-02-18 criteria provided, single submitter clinical testing
Invitae RCV000651069 SCV000772918 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 147 of the B3GALNT2 protein (p.Val147Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs143983025, ExAC 0.03%). This variant has not been reported in the literature in individuals with B3GALNT2-related disease. ClinVar contains an entry for this variant (Variation ID: 210513). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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