ClinVar Miner

Submissions for variant NM_000382.3(ALDH3A2):c.25_50del (p.Arg9fs) (rs767751416)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412337 SCV000486581 likely pathogenic Sjögren-Larsson syndrome 2016-06-27 criteria provided, single submitter clinical testing
Invitae RCV000791516 SCV000930768 pathogenic not provided 2018-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg9Alafs*36) in the ALDH3A2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to segregate with Sjögren-Larsson syndrome in a family (PMID: 29183715). ClinVar contains an entry for this variant (Variation ID: 371103). Loss-of-function variants in ALDH3A2 are known to be pathogenic (PMID: 10577908, 10854114). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000412337 SCV001363574 pathogenic Sjögren-Larsson syndrome 2019-12-16 criteria provided, single submitter clinical testing Variant summary: ALDH3A2 c.25_50del26 (p.Arg9AlafsX36) 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 194754 control chromosomes (gnomAD). c.25_50del26 has been reported in the literature in individuals affected with Sjogren-Larsson Syndrome (Willemsen_2001, Sanders_2008, Kariminejad_2017). These data indicate that the variant may be associated with disease. Sanders_2008 reports this variant has an impact on protein function and results in decreasing activity from patients fibroblast cells. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Rizzo Lab,University of Nebraska Medical Center RCV000412337 SCV000598619 pathogenic Sjögren-Larsson syndrome 2017-06-01 no assertion criteria provided research
Natera, Inc. RCV000412337 SCV001459269 pathogenic Sjögren-Larsson syndrome 2020-09-16 no assertion criteria provided clinical testing

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