ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.862_863TG[2] (p.Val289fs) (rs180177321)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated 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 2019-12-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GRHPR gene (p.Val289Aspfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acids of the GRHPR protein. This variant is present in population databases (rs768997865, ExAC 0.03%). This variant has been observed in several individuals affected with primary hyperoxaluria type 2 (PMID: 24116921, 11728965). This variant is also known as 862delTG in the literature. 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: 24116921, 14635115). 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.
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

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