Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255515 | SCV000322393 | pathogenic | not provided | 2023-05-11 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that the D245N variant almost completely abolishes the enzymatic activity of the protein (Rizzo et al., 1999); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21872273, 11408337, 10577908, 11306053, 9829906, 16996289, 15931689, 29183715) |
Broad Center for Mendelian Genomics, |
RCV000663418 | SCV000786717 | pathogenic | Sjögren-Larsson syndrome | criteria provided, single submitter | research | The homozygous p.Asp245Asn variant was identified by our study in two individuals with Sjogren-Larsson Syndrome. The p.Asp245Asn variant is believed to be pathogenic based on numberous reports in the literature and databases. | |
Invitae | RCV000255515 | SCV000949868 | pathogenic | not provided | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 245 of the ALDH3A2 protein (p.Asp245Asn). This variant is present in population databases (rs72547568, gnomAD 0.002%). This missense change has been observed in individual(s) with Sjoegren-Larsson syndrome (PMID: 10577908, 11408337, 21872273). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant has also been described in the literature as part of a complex haplotype in individuals affected with Sjoegren-Larsson syndrome with European heritage (PMID: 29183715, 9829906). In these individuals this variant is described in combination with a complex variant involving three separate sequence changes that occur on the same chromosome (in cis) (c.901 G>C; c.906delT; and c.909 T>G). ClinVar contains an entry for this complex haplotype (Variation ID: 438264). ClinVar contains an entry for this variant (Variation ID: 265459). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ALDH3A2 protein function. Experimental studies have shown that this missense change affects ALDH3A2 function (PMID: 10577908). In summary, this is a rare variant that has been observed as part of a complex European haplotype with a second pathogenic variant. It has been observed in several individuals with Sjögren-Larsson syndrome, and is expected to affect ALDH3A2 protein function. For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000255515 | SCV002545898 | likely pathogenic | not provided | 2022-04-01 | criteria provided, single submitter | clinical testing | ALDH3A2: PM2, PM3, PS4:Moderate, PS3:Supporting, BP2 |
Counsyl | RCV000663418 | SCV000789733 | likely pathogenic | Sjögren-Larsson syndrome | 2019-04-09 | no assertion criteria provided | clinical testing | |
Genome |
RCV000663418 | SCV002074936 | not provided | Sjögren-Larsson syndrome | no assertion provided | phenotyping only | Variant interpreted as Pathogenic and reported on 01-10-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. | |
Natera, |
RCV000663418 | SCV002093180 | pathogenic | Sjögren-Larsson syndrome | 2020-12-31 | no assertion criteria provided | clinical testing |