Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000411163 | SCV000486715 | pathogenic | Sjögren-Larsson syndrome | 2016-07-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000411163 | SCV000918410 | pathogenic | Sjögren-Larsson syndrome | 2018-08-23 | criteria provided, single submitter | clinical testing | Variant summary: ALDH3A2 c.798+1delG is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site, while another predicts the weakening of a 5' donor site. These predictions are supported by RT-PCR assays that revealed aberrant splicing in a homozygous patient's fibroblasts and FALDH enzyme activity assays showing activity levels of <10% of controls (Rizzo_1999, Rizzo_2010). The variant allele was found at a frequency of 8.9e-06 in 112548 control chromosomes (ExAC). The variant, c.798+1delG, has been reported in the literature in multiple individuals affected with Sjogren-Larsson Syndrome (Rizzo_1999, Rizzo_2010). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001231409 | SCV001403929 | pathogenic | not provided | 2023-09-20 | criteria provided, single submitter | clinical testing | This sequence change affects a splice site in intron 5 of the ALDH3A2 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 ALDH3A2 are known to be pathogenic (PMID: 10577908, 10854114). This variant is present in population databases (rs757359379, gnomAD 0.006%). Disruption of this splice site has been observed in individuals with Sjögren-Larsson syndrome (PMID: 10577908, 30157790). ClinVar contains an entry for this variant (Variation ID: 371195). Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 10577908). For these reasons, this variant has been classified as Pathogenic. |
Natera, |
RCV000411163 | SCV001459272 | pathogenic | Sjögren-Larsson syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |