ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.404+3_404+6del (rs180177309)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000186457 SCV000919477 pathogenic Primary hyperoxaluria, type II 2018-08-03 criteria provided, single submitter clinical testing Variant summary: GRHPR c.404+3_404+6delAAGT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 5 splicing donor site. These predictions have been confirmed by experimental evidence that this variant affects mRNA splicing (Cregeen_2003). The variant allele was found at a frequency of 2.8e-05 in 246140 control chromosomes. c.404+3_404+6delAAGT has been reported in the literature in multiple individuals affected with Primary Hyperoxaluria Type 2, and has been reported as a common pathogenic variants in individuals of Asian ancestry (Cregeen_2003, Webster_2000, Williams_2014). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Myriad Women's Health, Inc. RCV000186457 SCV001194179 likely pathogenic Primary hyperoxaluria, type II 2019-12-19 criteria provided, single submitter clinical testing NM_012203.1(GRHPR):c.404+3_404+6delAAGT is classified as likely pathogenic in the context of primary hyperoxaluria type 2. Sources cited for classification include the following: PMID 24116921 and 14635115. Classification of NM_012203.1(GRHPR):c.404+3_404+6delAAGT is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations and the incidence of disease is extremely low. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV001057355 SCV001221842 pathogenic not provided 2019-10-31 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the GRHPR gene. It does not directly change the encoded amino acid sequence of the GRHPR protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs180177309, ExAC 0.006%). This variant has been observed in individuals affected with primary hyperoxaluria type 2 (PMID: 11030416, 14635115). This variant is also known as c.403_405+2delAAGT in the literature. ClinVar contains an entry for this variant (Variation ID: 204250). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 14635115). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000186457 SCV000041223 pathologic Primary hyperoxaluria, type II 2011-05-05 no assertion criteria provided curation Converted during submission to Pathogenic.
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000186457 SCV000239804 pathogenic Primary hyperoxaluria, type II 2014-11-27 no assertion criteria provided research
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000186457 SCV000239814 pathogenic Primary hyperoxaluria, type II 2014-11-27 no assertion criteria provided research
Myriad Women's Health, Inc. RCV000186457 SCV000485235 likely pathogenic Primary hyperoxaluria, type II 2016-01-05 no assertion criteria provided clinical testing

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