ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.734+1G>A

gnomAD frequency: 0.00006  dbSNP: rs148049120
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000805272 SCV000945221 pathogenic not provided 2023-12-30 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 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 present in population databases (rs148049120, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of GRHPR-related conditions (PMID: 25644115; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 650172). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001784426 SCV002018527 likely pathogenic Primary hyperoxaluria, type II 2022-01-26 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001784426 SCV002060114 likely pathogenic Primary hyperoxaluria, type II 2021-11-10 criteria provided, single submitter clinical testing NM_012203.1(GRHPR):c.734+1G>A is a canonical splice variant classified as likely pathogenic in the context of primary hyperoxaluria type 2. c.734+1G>A has been observed in cases with relevant disease (PMID: 25644115). Functional assessments of this variant are not available in the literature. c.734+1G>A has been observed in population frequency databases (gnomAD: NFE <0.001%). In summary, NM_012203.1(GRHPR):c.734+1G>A is a canonical splice variant in a gene where loss of function is a known mechanism of disease and is predicted to disrupt protein function. Please note: this variant was assessed in the context of healthy population screening.
Fulgent Genetics, Fulgent Genetics RCV001784426 SCV002800600 likely pathogenic Primary hyperoxaluria, type II 2021-08-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV001784426 SCV004191696 pathogenic Primary hyperoxaluria, type II 2023-10-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV001784426 SCV002075686 likely pathogenic Primary hyperoxaluria, type II 2020-08-13 no assertion criteria provided clinical testing

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