Submissions for variant NM_000382.3(ALDH3A2):c.901_903delinsCC (p.Ala301fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169619	SCV000221146	likely pathogenic	Sjögren-Larsson syndrome	2015-02-19	criteria provided, single submitter	literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169619	SCV001339058	pathogenic	Sjögren-Larsson syndrome	2021-04-26	criteria provided, single submitter	clinical testing	Variant summary: ALDH3A2 c.901_903delinsCC (p.Ala301ProfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 282830 control chromosomes. c.901_903delinsCC has been reported in the literature with a legacy nomenclature of c.901G>C and c.906delT in individuals affected with Sjogren-Larsson Syndrome (example, Sillen_1998, Keller_2010). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal fatty aldehyde dehydrogenase enzyme activity in patient fibroblasts (example, Keller_2010). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.