ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.866_867del (p.Val289fs)

dbSNP: rs180177321
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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, 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, Mayo Clinic 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 2023-10-31 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, Health Services Laboratory RCV000149441 SCV000239818 pathogenic Primary hyperoxaluria, type II 2014-11-27 no assertion criteria provided research
Natera, Inc. RCV000149441 SCV002075694 pathogenic Primary hyperoxaluria, type II 2021-03-10 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.