ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.84-2A>G

dbSNP: rs180177319
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000186448 SCV000789081 pathogenic Primary hyperoxaluria, type II 2016-12-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000186448 SCV000919476 pathogenic Primary hyperoxaluria, type II 2017-09-25 criteria provided, single submitter clinical testing Variant summary: The GRHPR c.84-2A>G variant involves the alteration of a conserved intronic nucleotide within the splice acceptor site of intron 1. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict a significant impact on normal splicing. One functional study found that this variant is affecting splicing causing exon 2 skipping and negligible catalytic and immunoreactivity in the liver biopsy of a primary hyperoxaluria type 2 (PH2) patient (Cregeen_2003). The variant was not found in the control population dataset of gnomAD in 273564 control chromosomes and was reported in two PH2 patients in the literature (Cregeen_2003). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001857597 SCV002241929 pathogenic not provided 2022-04-17 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 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 not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with primary hyperoxaluria type 2 (PMID: 14635115). ClinVar contains an entry for this variant (Variation ID: 204241). Studies have shown that disruption of this splice site is associated with altered splicing resulting in unknown protein product impact (PMID: 14635115). For these reasons, this variant has been classified as Pathogenic.
Clinical Biochemistry Laboratory, Health Services Laboratory RCV000186448 SCV000239803 pathogenic Primary hyperoxaluria, type II 2014-11-27 no assertion criteria provided research

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