Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000805272 | SCV000945221 | pathogenic | not provided | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 7 of the GRHPR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GRHPR are known to be pathogenic (PMID: 25644115). This variant is present in population databases (rs148049120, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of GRHPR-related conditions (PMID: 25644115; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 650172). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV001784426 | SCV002018527 | likely pathogenic | Primary hyperoxaluria, type II | 2022-01-26 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV001784426 | SCV002060114 | likely pathogenic | Primary hyperoxaluria, type II | 2021-11-10 | criteria provided, single submitter | clinical testing | NM_012203.1(GRHPR):c.734+1G>A is a canonical splice variant classified as likely pathogenic in the context of primary hyperoxaluria type 2. c.734+1G>A has been observed in cases with relevant disease (PMID: 25644115). Functional assessments of this variant are not available in the literature. c.734+1G>A has been observed in population frequency databases (gnomAD: NFE <0.001%). In summary, NM_012203.1(GRHPR):c.734+1G>A is a canonical splice variant in a gene where loss of function is a known mechanism of disease and is predicted to disrupt protein function. Please note: this variant was assessed in the context of healthy population screening. |
Fulgent Genetics, |
RCV001784426 | SCV002800600 | likely pathogenic | Primary hyperoxaluria, type II | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001784426 | SCV004191696 | pathogenic | Primary hyperoxaluria, type II | 2024-03-19 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001784426 | SCV002075686 | likely pathogenic | Primary hyperoxaluria, type II | 2020-08-13 | no assertion criteria provided | clinical testing |