ClinVar

Description

The PKD2 p.Gln300His variant was not identified in the literature nor was it identified in ClinVar, LOVD3.0, ADPKD-MD or ADPKD-LOVD2.0. The variant was identified in dbSNP (rs1394365736) as “NA”. The variant was identified in control databases in 2 of 251,192 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the East Asian population in 2 of 18,394 chromosomes (freq: 0.0001) but not in the African, Latino, Ashkenazi Jewish, Finnish, European, Other or South Asian populations. The p.Gln300 residue is conserved in in mammals but not in more distantly related organisms however computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; 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.