ClinVar Miner

Submissions for variant NM_000392.5(ABCC2):c.3449G>A (p.Arg1150His)

gnomAD frequency: 0.00009  dbSNP: rs72558200
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV000008930 SCV002023916 likely pathogenic Dubin-Johnson syndrome 2020-07-22 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003421913 SCV004118106 pathogenic ABCC2-related disorder 2023-07-30 criteria provided, single submitter clinical testing The ABCC2 c.3449G>A variant is predicted to result in the amino acid substitution p.Arg1150His. This variant has been reported in the compound heterozygous state in two sibling with Dubin-Johnson syndrome, and also in the homozygous state in 5 individuals from 4 families with Dubin-Johnson syndrome (Mor-Cohen et al. 2001. PubMed ID: 11477083). In vitro functional studies suggest that this variant impairs the transport activity of ABCC2 (Mor-Cohen et al. 2001. PubMed ID: 11477083). This variant is interpreted as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003574699 SCV004354556 pathogenic not provided 2024-02-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1150 of the ABCC2 protein (p.Arg1150His). This variant is present in population databases (rs72558200, gnomAD 0.01%). This missense change has been observed in individual(s) with Dubin-Johnson syndrome (PMID: 11477083). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8419). 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 not expected to disrupt ABCC2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ABCC2 function (PMID: 11477083). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000008930 SCV005664894 likely pathogenic Dubin-Johnson syndrome 2024-05-01 criteria provided, single submitter clinical testing
OMIM RCV000008930 SCV000029140 pathogenic Dubin-Johnson syndrome 2001-10-05 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.