Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169182 | SCV000220421 | likely pathogenic | Sjögren-Larsson syndrome | 2014-06-17 | criteria provided, single submitter | literature only | |
Illumina Laboratory Services, |
RCV000169182 | SCV000914756 | uncertain significance | Sjögren-Larsson syndrome | 2018-03-07 | criteria provided, single submitter | clinical testing | The ALDH3A2 c.28C>T (p.Gln10Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein and has been reported in a heterozygous state in a Spanish individual with Sjogren-Larsson syndrome (Rizzo et al. 1999). Cultured skin fibroblasts from this individual were shown to be deficient in FALDH, but the individual's full genotype was not clearly reported. In addition, Sanabria and Coco (2011) report the p.Gln10Ter variant in a heterozygous state in two siblings with Sjogren-Larsson syndrome who were also heterozygous for an in-frame deletion variant; the phase of the variants in these individuals was not reported. Control data are unavailable for the p.Gln10Ter variant, which is reported at a frequency of 0.000383 in the East Asian population of the Exome Aggregation Consortium. However, this frequency is based on only one allele in a region of poor sequence coverage. Based on the limited evidence available and the potential impact of stop-gained variants, the p.Gln10Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for Sjogren-Larsson syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV001041547 | SCV001205171 | pathogenic | not provided | 2023-06-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 188833). This premature translational stop signal has been observed in individual(s) with Sjogren-Larsson syndrome (PMID: 10577908, 21968182). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gln10*) in the ALDH3A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALDH3A2 are known to be pathogenic (PMID: 10577908, 10854114). |
Natera, |
RCV000169182 | SCV002093174 | pathogenic | Sjögren-Larsson syndrome | 2021-10-20 | no assertion criteria provided | clinical testing |