ClinVar Miner

Submissions for variant NM_000382.3(ALDH3A2):c.472-2A>G

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670121 SCV000794938 likely pathogenic Sjögren-Larsson syndrome 2017-10-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000670121 SCV001478642 pathogenic Sjögren-Larsson syndrome 2021-01-25 criteria provided, single submitter clinical testing Variant summary: ALDH3A2 c.472-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing resulting in an in-frame deletion of the first 33 nucleotides within exon 4 of the mRNA and a predicted loss of 11 amino acids from the FALDH protein. The variant was absent in 251306 control chromosomes. c.472-2A>G has been reported in the literature in at-least one individual affected with Sjogren-Larsson Syndrome (example, Rizzo_1999) and has been subsequently cited by others. These data do not allow any conclusion about variant significance. 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 likely pathogenic citing an overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.

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