Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002541811 | SCV003012349 | likely benign | Autosomal recessive polycystic kidney disease | 2024-01-28 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001292251 | SCV001481098 | uncertain significance | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKHD1 c.3561-11A>G variant was not identified in the literature nor was it identified in the ClinVar, LOVD 3.0 and RWTH AAachen University ARPKD database. The variant was also identified in dbSNP (ID: rs774114631) as “NA”. The variant was identified in control databases in 9 of 277066 chromosomes at a frequency of 0.000032 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include Latino in 2 of 34410 chromosomes (freq: 0.00006), European Non-Finnish in 4 of 126612 chromosomes (freq: 0.000032), and South Asian in 3 of 30778 chromosomes (freq: 0.0001). While the variant was not observed in the African, other, Ashkenazi Jewish, East Asian, European Finnish, populations. The c.3561-11A>G variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. 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. This variant is classified as a variant of uncertain significance. |