Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479678 | SCV004223277 | uncertain significance | not specified | 2023-11-30 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.1124G>A (p.Arg375Gln) results in a conservative amino acid change located in the PA14/GLEYA domain (IPR037524) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251142 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1124G>A has been reported in the literature in the heterozygous state in an individual who met the study diagnostic criteria for polycystic kidney disease with 3 cysts at age 25, and it was also found in the heterozygous state in the mother who did not meet diagnostic criteria, having only one cyst at the age of 55 (Yu_2022). This report does not provide unequivocal conclusions about association of the variant with Polycystic Kidney And Hepatic Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35778421). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |