ClinVar Miner

Submissions for variant NM_138413.4(HOGA1):c.208C>T (p.Arg70Ter)

gnomAD frequency: 0.00002  dbSNP: rs758304537
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Biochemistry Laboratory, Health Services Laboratory RCV000186476 SCV000239835 pathogenic Primary hyperoxaluria type 3 2023-10-27 criteria provided, single submitter clinical testing ACMG: PVS1 PM2 PM3
Counsyl RCV000186476 SCV000790723 pathogenic Primary hyperoxaluria type 3 2017-04-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000186476 SCV000893856 pathogenic Primary hyperoxaluria type 3 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000186476 SCV000914473 uncertain significance Primary hyperoxaluria type 3 2018-12-04 criteria provided, single submitter clinical testing The HOGA1 c.208C>T (p.Arg70Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Arg70Ter variant has been reported in one study in which it is found in a compound heterozygous state with another null variant on the second allele in two individuals with primary hyperoxaluria type III (Williams et al. 2012). Control data are unavailable for this variant, which is reported at a frequency of 0.000098 in the South Asian population from the Genome Aggregation Database. Based on the evidence and potential impact of stop-gained variants, the p.Arg70Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for primary hyperoxaluria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000795411 SCV000934874 pathogenic not provided 2023-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg70*) in the HOGA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HOGA1 are known to be pathogenic (PMID: 22391140, 22781098). This variant is present in population databases (rs758304537, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with primary hyperoxaluria type 3 (PMID: 22391140, 25629080, 27742850). ClinVar contains an entry for this variant (Variation ID: 204269). For these reasons, this variant has been classified as Pathogenic.
3billion RCV000186476 SCV002520944 pathogenic Primary hyperoxaluria type 3 2022-05-22 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). The variant has been reported to be associated with HOGA1 related disorder (ClinVar ID: VCV000204269 / PMID: 22391140). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000186476 SCV004171970 pathogenic Primary hyperoxaluria type 3 2023-01-24 criteria provided, single submitter clinical testing The missense c.208C>T (p.Arg70Ter) variant in HOGA1 gene has been reported previously in compound heterozygous state in individuals affected with primary hyperoxaluria type III (Williams et al. 2012; Williams et al. 2015; Richard et al. 2017). The c.208C>T variant is reported with an allele frequency of 0.004% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain Significance / Pathognic (multiple submissions). The nucleotide change c.208C>T in HOGA1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV000186476 SCV002094526 pathogenic Primary hyperoxaluria type 3 2020-09-10 no assertion criteria provided clinical testing

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