Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588010 | SCV000699331 | pathogenic | Primary hyperoxaluria | 2016-06-17 | criteria provided, single submitter | clinical testing | Variant summary: The GRHPR c.864_865delTG (p.Val289Aspfs) variant results in a premature termination codon, predicted to cause a truncated or absent GRHPR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 3/121702 control chromosomes at a frequency of 0.0000247, which does not exceed the estimated maximal expected allele frequency of a pathogenic GRHPR variant (0.0014434). It was only found in East Asian population in which allele frequency was 0.033% (3/9124 chromosomes). This variant has been reported in five PH2 patients of East Asian origin including four patients who carried this variant in homozygous state (Takayama_2014). The authors recommend that this mutation, particularly in patients of East Asian origin, should be screened when PH2 is suspected. Multiple labs/reputable databases classify this variant as pathogenic. Taken together, this variant is classified as Pathogenic. |
| Invitae | RCV001041549 | SCV001205173 | pathogenic | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val289Aspfs*22) in the GRHPR gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acid(s) of the GRHPR protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with primary hyperoxaluria type 2 (PMID: 11728965, 24116921). This variant is also known as 862delTG. ClinVar contains an entry for this variant (Variation ID: 162020). This variant disrupts the p.Arg302 amino acid residue in GRHPR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14635115, 24116921). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000149441 | SCV002811080 | pathogenic | Primary hyperoxaluria, type II | 2022-01-14 | criteria provided, single submitter | clinical testing | |
| Rare Kidney Stone Consortium and the Mayo Clinic Hyperoxaluria Center, |
RCV000149441 | SCV004171753 | pathogenic | Primary hyperoxaluria, type II | 2023-10-27 | criteria provided, single submitter | clinical testing | ACMG:PVS1 PM2 PM3 PP4 |
| Baylor Genetics | RCV000149441 | SCV004191692 | pathogenic | Primary hyperoxaluria, type II | 2024-03-05 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000149441 | SCV000196079 | pathogenic | Primary hyperoxaluria, type II | 2014-10-01 | no assertion criteria provided | literature only | |
| Counsyl | RCV000149441 | SCV000220476 | likely pathogenic | Primary hyperoxaluria, type II | 2017-01-25 | no assertion criteria provided | clinical testing | |
| Clinical Biochemistry Laboratory, |
RCV000149441 | SCV000239818 | pathogenic | Primary hyperoxaluria, type II | 2014-11-27 | no assertion criteria provided | research | |
| Natera, |
RCV000149441 | SCV002075694 | pathogenic | Primary hyperoxaluria, type II | 2021-03-10 | no assertion criteria provided | clinical testing |