Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000595582 | SCV000706218 | likely pathogenic | not provided | 2017-02-06 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003465343 | SCV004217515 | pathogenic | Benign recurrent intrahepatic cholestasis type 2 | 2024-03-04 | criteria provided, single submitter | clinical testing | |
| Broad Center for Mendelian Genomics, |
RCV003319383 | SCV005907568 | likely pathogenic | Progressive familial intrahepatic cholestasis type 2 | 2025-02-03 | criteria provided, single submitter | curation | The p.Glu135Lys variant in ABCB11 has been reported in five individuals with BSEP deficiency (PMID: 19101985, 26678486, 28733223, 35626323; CebecauerovaÃÅ et al. 2010), and has been identified in 0.004% (48/1148100) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs752992432). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID: 500323) and has been interpreted as likely pathogenic by Genomics And Bioinformatics Analysis Resource (Columbia University) and Eurofins Ntd Llc (ga). Of the five affected individuals, two were compound heterozygotes that carried a reported pathogenic variant in trans and one was a compound heterozygote that carried a reported pathogenic variant with unknown phase, which increases the likelihood that the p.Glu135Lys variant is pathogenic (Variation ID: 374098, 6590; PMID: 26678486, 28733223, 35626323). In vitro functional studies provide some evidence that the p.Glu135Lys variant may slightly impact protein function (PMID: 19101985). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive BSEP deficiency. ACMG/AMP Criteria applied: PM3_strong, PP3, PM2_supporting, PS3_supporting (Richards 2015). |
| Genomics And Bioinformatics Analysis Resource, |
RCV003319383 | SCV004024090 | likely pathogenic | Progressive familial intrahepatic cholestasis type 2 | no assertion criteria provided | research |