Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV000499946 | SCV000592725 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 c.-67C>T variant was identified in the literature in infant with ADPKD with co-occurring certain pathogenic variant PKD1 (c.8362_8363ins34) (Gilbert 2013), and in one individual in our laboratory with pathogenic variant in PKD2 (c.1663C>T (p.Gln555*)), increasing the likelihood that the c.-67C>T variant does not have clinical significance. The variant was also identified in dbSNP (ID: rs1016465177) as "With Likely benign allele", ClinVar (classified as likely benign by one submitter), and ADPKD Mutation Database (as likely neutral). The variant was identified in control databases in 123 of 25272 chromosomes at a frequency of 0.0049 (Genome Aggregation Database Feb 27, 2017), and observed in the following populations: African in 123 of 8194 chromosomes (freq: 0.015), European in 2 of 13610 chromosomes (freq. 0.00014), while not observed in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |