Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV002493527 | SCV002803244 | uncertain significance | Polycystic kidney disease, adult type | 2021-11-04 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001292018 | SCV001481093 | uncertain significance | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Ile2716Val variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, LOVD 3.0, ADPKD Mutation Database, or PKD1-LOVD, databases. The variant was identified in control databases in 5 of 147200 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 4 of 24508 chromosomes (freq: 0.0002), European in 1 of 57092 chromosomes (freq: 0.00002), while the variant was not observed in the African, Other, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The p.Ile2716 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of 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. |