ClinVar

Description

The MAN2B1 p.Glu910Lys variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs139366493) and LOVD 3.0 (variant effect not shared). The variant was identified in control databases in 34 of 281492 chromosomes at a frequency of 0.0001208 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 32 of 127876 chromosomes (freq: 0.00025) and African in 2 of 24920 chromosomes (freq: 0.00008), but was not observed in the Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Glu910 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.