ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.295C>T (p.Arg99Ter) (rs119490108)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000005991 SCV000239793 pathogenic Primary hyperoxaluria, type II 2014-11-27 no assertion criteria provided research
GeneDx RCV000579200 SCV000680775 pathogenic not provided 2017-11-02 criteria provided, single submitter clinical testing The R99X variant in the GRHPR gene has been reported previously in association with primary hyperoxaluria type 2, in affected individuals who were homozygous for the R99X variant or who were heterozygous for the R99X variant and another variant (Webster et al., 2000; Cregeen et al., 2003; Williams et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R99X variant is observed in 2/30782 (0.006%) alleles from individuals of South Asian background, including 1 homozygous individual in large population cohorts (Lek et al., 2016). We interpret R99X as a pathogenic variant.
GenomeConnect, ClinGen RCV000005991 SCV000840174 not provided Primary hyperoxaluria, type II no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Integrated Genetics/Laboratory Corporation of America RCV000590094 SCV000699329 pathogenic Primary hyperoxaluria 2016-09-16 criteria provided, single submitter clinical testing Variant summary: The GRHPR c.295C>T (p.Arg99X) 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. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple clinical laboratories/databases cite the variant as "pathogenic." Therefore, the variant of interest has been classified as Pathogenic.
Invitae RCV000579200 SCV000943618 pathogenic not provided 2018-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg99*) in the GRHPR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another GRHPR variant in several individuals affected with primary hyperoxaluria (PMID: 11030416, 14635115, 25629080). ClinVar contains an entry for this variant (Variation ID: 5637). Loss-of-function variants in GRHPR are known to be pathogenic (PMID: 25644115). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005991 SCV000026173 pathogenic Primary hyperoxaluria, type II 2000-08-01 no assertion criteria provided literature only

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