Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002234746 | SCV000942486 | likely pathogenic | Wolman disease | 2023-01-26 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 648013). This variant has not been reported in the literature in individuals affected with LIPA-related conditions. This variant is present in population databases (rs762960877, gnomAD 0.002%). This sequence change affects a donor splice site in intron 2 of the LIPA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LIPA are known to be pathogenic (PMID: 23485521). |
| Victorian Clinical Genetics Services, |
RCV003225126 | SCV003921865 | pathogenic | Lysosomal acid lipase deficiency | 2022-02-23 | criteria provided, single submitter | clinical testing | 0102 - Loss of function is a known mechanism of disease in this gene and is associated with cholesteryl ester storage disease (CEST) and Wolman disease (MIM#278000). (I) 0106 - This gene is associated with autosomal recessive disease. (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 (2 heterozygotes, 0 homozygotes). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another canonical splice site variant comparable to the one identified in this case has limited previous evidence for pathogenicity. A different variant in the same canonical splice site, c.111+2T>G, has been reported as likely pathogenic in ClinVar. (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been submitted once as likely pathogenic to ClinVar. (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) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |