Submissions for variant NM_001139.3(ALOX12B):c.416_417del (p.Ala139fs)

dbSNP: rs1977208852

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265978	SCV002548147	likely pathogenic	Lamellar ichthyosis	2022-05-04	criteria provided, single submitter	clinical testing	Variant summary: ALOX12B c.416_417delCC (p.Ala139GlufsX37) 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 reported in affected individuals (HGMD). The variant was absent in 250612 control chromosomes (gnomAD). c.416_417delCC has been reported in the literature in a homozygous individual affected with congenital ichthyosis, however no further phenotype details were provided (Hotz_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One submitter has provided clinical-significance assessments for this variant in 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 likely pathogenic.
Institute for Human Genetics, University Medical Center Freiburg	RCV001289974	SCV001477987	pathogenic	Autosomal recessive congenital ichthyosis 2	2021-01-07	no assertion criteria provided	clinical testing