Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000734633 | SCV000862789 | uncertain significance | not provided | 2018-08-07 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000734633 | SCV003451318 | pathogenic | not provided | 2024-03-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 693 of the ABCC2 protein (p.Gly693Arg). This variant is present in population databases (rs765570396, gnomAD 0.01%). This missense change has been observed in individuals with Dubin-Johnson syndrome (PMID: 31544333, 32183854). ClinVar contains an entry for this variant (Variation ID: 598277). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCC2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ABCC2 function (PMID: 32183854). For these reasons, this variant has been classified as Pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV004720281 | SCV005329623 | pathogenic | Dubin-Johnson syndrome | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense c.2077G>A(p.Gly693Arg) variant in ABCC2 gene has been reported previously in individuals affected with Dubin-Johnson syndrome (Liu T, et al., 2023; Wu L, et al., 2020; Corpechot C, et al., 2020). Experimental studies have shown that this missense change affects ABCC2 function (Wu L, et al., 2020). The p.Gly693Arg variant has been reported with allele frequency of 0.004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance / Pathogenic. The amino acid change p.Gly693Arg in ABCC2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 693 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidences (Polyphen - Probably damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. For these reasons, this variant has been classified as Pathogenic. |
| Mayo Clinic Laboratories, |
RCV000734633 | SCV005413958 | pathogenic | not provided | 2023-07-07 | criteria provided, single submitter | clinical testing | PP3, PM2_moderate, PS3, PS4 |
| Prevention |
RCV004745575 | SCV005350721 | pathogenic | ABCC2-related disorder | 2024-05-03 | no assertion criteria provided | clinical testing | The ABCC2 c.2077G>A variant is predicted to result in the amino acid substitution p.Gly693Arg. This variant has been reported in an individual with autosomal recessive Dubin-Johnson syndrome and functional in vitro studies showed this variant led to decreased expression, mislocalization and decreased organic anion transport activity of the ABCC2 encoded MPR2 protein (Wu et al. 2018. PubMed ID: 30344695; Wu et al. 2020. PubMed ID: 32183854). This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as pathogenic. |