Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000593882 | SCV000708434 | uncertain significance | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001082366 | SCV001001785 | likely benign | Autosomal recessive polycystic kidney disease | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174910 | SCV001338343 | uncertain significance | not specified | 2020-02-29 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.2280-10C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00021 in 251258 control chromosomes, predominantly at a frequency of 0.0012 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2280-10C>T in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV001082366 | SCV001463501 | uncertain significance | Autosomal recessive polycystic kidney disease | 2017-11-16 | no assertion criteria provided | clinical testing |