ClinVar Miner

Submissions for variant NM_000392.5(ABCC2):c.3196C>T (p.Arg1066Ter)

gnomAD frequency: 0.00053  dbSNP: rs72558199
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725912 SCV000340472 pathogenic not provided 2018-06-22 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000024307 SCV000359797 likely pathogenic Dubin-Johnson syndrome 2017-04-27 criteria provided, single submitter clinical testing The ABCC2 c.3196C>T (p.Arg1066Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Arg1066Ter variant has been reported in two studies in which it is found in a total of three individuals with Dubin-Johnson syndrome including in one in a homozygous state and in two siblings in a compound heterozygous state (Paulusma et al. 1997; Pacifico et al. 2010). Control data are unavailable for this variant, which is reported at a frequency 0.00139 in the European American population of the Exome Sequencing Project. Based on the potential impact of stop-gained variants and the evidence from the literature, the p.Arg1066Ter variant is classified as likely pathogenic for Dubin-Johnson syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
CeGaT Center for Human Genetics Tuebingen RCV000725912 SCV001250384 pathogenic not provided 2019-12-01 criteria provided, single submitter clinical testing
Invitae RCV000725912 SCV002232583 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1066*) in the ABCC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCC2 are known to be pathogenic (PMID: 9185779, 16549534, 16952291). This variant is present in population databases (rs72558199, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individuals with Dubin-Johnson syndrome (PMID: 9185779, 10464142, 21044052). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31603). 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.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000024307 SCV004048237 likely pathogenic Dubin-Johnson syndrome criteria provided, single submitter clinical testing The ABCC2 c.3196C>T (p.Arg1066Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Arg1066Ter variant has been reported in two studies in which it is found in a total of three individuals with Dubin-Johnson syndrome including in one in a homozygous state and in two siblings in a compound heterozygous state (Paulusma et al. 1997; Pacifico et al. 2010). The p.Arg1066Ter variant is reported with the allele frequency of 0.04% in gnomAD Exome and is novel (not in any individuals) in 1000 GenomesThis variant has been reported to the ClinVar database as Pathogenic/Likely_pathogenic with a status of criteria provided, multiple submitters, no conflicts. The nucleotide change in ABCC2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely pathogenic.
PreventionGenetics, part of Exact Sciences RCV003415739 SCV004116774 pathogenic ABCC2-related condition 2024-01-31 criteria provided, single submitter clinical testing The ABCC2 c.3196C>T variant is predicted to result in premature protein termination (p.Arg1066*). This variant has been reported to be causative for autosomal recessive Dubin-Johnson syndrome (Paulusma et al. 1997. PubMed ID: 9185779; Pacifico et al. 2010. PubMed ID: 21044052; Corpechot et al. 2020. PubMed ID: 31544333). This variant is reported in 0.06% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in ABCC2 are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM RCV000024307 SCV000045598 pathogenic Dubin-Johnson syndrome 2010-12-01 no assertion criteria provided literature only

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