Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002493541 | SCV002802915 | likely benign | Polycystic kidney disease, adult type | 2021-12-08 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001292424 | SCV001480877 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Ala568= variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, LOVD 3.0, ADPKD Mutation Database, PKD1-LOVD, databases. The variant was identified in control databases in 3 of 30916 chromosomes at a frequency of 0.000097 in the following population: African in 3 of 8706 chromosomes (freq. 0.00034), increasing the likelihood that this may be a low frequency variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. This variant was also identified in our laboratory in one individual with ADPKD, co-occurring pathogenic PKD1 variant (c.8017-?_8161+?del), increasing the likelihood that the p. Ala568= variant does not have clinical significance. The p.Ala568Ala 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 the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |