Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neurogenetics Research Program, |
RCV001794427 | SCV001737595 | pathogenic | Cerebral palsy | 2021-06-10 | criteria provided, single submitter | research | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000001705 | SCV002819866 | pathogenic | Sjögren-Larsson syndrome | 2022-12-28 | criteria provided, single submitter | clinical testing | Variant summary: ALDH3A2 c.941_943delinsGGGCTAAAAGTACTGTTGGGG (p.Ala314_Pro315delinsGlyAlaLysSerThrValGlyAla) results in an in-frame deletion/insertion that is predicted to delete 2 amino acids and insert 8 amino acids into the encoded protein. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The frequency of this variant in the general population could not be determined as the technology used for large population databases (ExAC, gnomAD, ESP, 1000G) cannot detect variants of this type. c.941_943delinsGGGCTAAAAGTACTGTTGGGG has been reported in the literature in individuals affected with Sjogren-Larsson Syndrome or related disorders. These data indicate that the variant may be associated with disease. At least two publications report that FALDH activity in patients carrying this variant is <10% of normal activity. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000001705 | SCV000021861 | pathogenic | Sjögren-Larsson syndrome | 1997-05-01 | no assertion criteria provided | literature only |