Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004789309 | SCV005398794 | likely pathogenic | Low phospholipid associated cholelithiasis | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with intrahepatic cholestasis of pregnancy, 3 (ICP-3; MIM#614972), low phospholipid-associated cholelithiasis (LPAC; MIM# 600803) and progressive familial intrahepatic cholestasis, 3 (PFIC; MIM#602347). (I) 0108 - This gene is associated with both recessive and dominant disease. PFIC is inherited in a recessive manner, whereas ICP-3 and LPAC can be either dominant or recessive. Biallelic variants typically demonstrate less residual protein activity, resulting in earlier onset of the condition with a more severe phenotype (OMIM, PMIDs: 24806754, 32376413). (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (1 heterozygote, 0 homozygotes). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another canonical splice variant comparable to the one identified in this case has limited previous evidence for pathogenicity. c.834-2A>G has been classified as pathogenic by a clinical laboratory in ClinVar. (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been observed with a missense variant, p.(Arg150Lys), in a large rare diseases cohort study, however, it is unclear if these two variants were in cis or in trans (PMID: 32581362). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited and to be in cis with NM_000443.3 (ABCB4):c.449G>A; p.(Arg150Lys). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Fulgent Genetics, |
RCV005047189 | SCV005674290 | likely pathogenic | Progressive familial intrahepatic cholestasis type 3; Low phospholipid associated cholelithiasis; Cholestasis, intrahepatic, of pregnancy, 3 | 2024-06-24 | criteria provided, single submitter | clinical testing | |
| NIHR Bioresource Rare Diseases, |
RCV001003561 | SCV001161922 | likely pathogenic | Cholestasis, intrahepatic, of pregnancy, 3 | no assertion criteria provided | research |