ClinVar Miner

Submissions for variant NM_001139.3(ALOX12B):c.1272dup (p.Lys425fs)

gnomAD frequency: 0.00004  dbSNP: rs763328506
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001262748 SCV001440730 pathogenic Autosomal recessive congenital ichthyosis 2 2020-09-04 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous with NM_001139.2:c.1144A>G.
GeneDx RCV001838469 SCV002098162 pathogenic not provided 2022-02-17 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31168818, 19131948, 23083690, 33435499)
Invitae RCV001838469 SCV002246447 pathogenic not provided 2022-07-16 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: 982978). This premature translational stop signal has been observed in individual(s) with congenital ichthyosis (PMID: 19131948, 23083690, 31168818). This variant is present in population databases (rs763328506, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Lys425Glnfs*24) in the ALOX12B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALOX12B are known to be pathogenic (PMID: 16116617, 23621129, 31046801).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226454 SCV003922788 pathogenic Lamellar ichthyosis 2023-03-09 criteria provided, single submitter clinical testing Variant summary: ALOX12B c.1272dupC (p.Lys425GlnfsX24) 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 in ClinVar and are reported in association with autosomal recessive ichthyosis in HGMD. The variant allele was found at a frequency of 1.6e-05 in 248932 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1272dupC has been reported in the literature in multiple individuals affected with Lamellar Ichthyosis (e.g., Eckl_2009, Osorio_2013, Hotz_2021). These data indicate that the variant is very likely to be associated with disease. Four ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute for Human Genetics, University Medical Center Freiburg RCV001262748 SCV001477407 pathogenic Autosomal recessive congenital ichthyosis 2 2021-01-07 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.