ClinVar

Description

The PKD2 p.Gly140Gly variant was identified as a polymorphism in 7 of 172 proband chromosomes (frequency: 0.041) from individuals or families with Autosomal Dominant Polycystic Kidney Disease and (Bataille 2011, Liu 2015). The variant was also identified in dbSNP (ID: rs2728118 “With Benign allele”, with a minor allele frequency of 0.1144 (573 of 5000 chromosomes in the 1000 Genomes Project). This variant was identified in the Exome Aggregation Consortium database (March 14, 2016) in 662 (27 homozygous) of 10588 chromosomes (freq. 0.06 ) in the following populations: East Asian in 32 of 130 chromosomes (freq. 0.25), Latino in 12 of 96 chromosomes (freq. 0.125), other in 10 of 120 chromosomes (freq. 0.08), European (Non-Finnish) in 194 of 2688 chromosomes (freq. 0.07), South Asian in 409 of 7348 chromosomes (freq. 0.06), and African in 5 of 206 chromosomes (freq. 0.02), but was not seen in the Finnish population, increasing the likelihood this could be a low frequency benign variant. In the ClinVar database the variant was identified as benign by Emory Genetics laboratory and in Clinvitae it was identified as benign by EmyClass. In the Mayo Clinic PKD database the variant was identified as likely neutral. In LOVD-PKD2 database the variant was identified 6X and as having no effect. In mRNA transcript analysis in the parents of one patient, the p.Gly140Gly variant occurred in trans to a variant (c.595_595+ 14del) that is predicted to affect splicing and is subjected to nonsense mediated decay (Liu 2015). The p.Gly140Gly variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign.