Submissions for variant NM_001139.3(ALOX12B):c.1859C>A (p.Pro620Gln)

dbSNP: rs780420901

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000414766	SCV000492858	pathogenic	Ichthyosis	2015-06-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005238969	SCV005884068	uncertain significance	not specified	2024-12-11	criteria provided, single submitter	clinical testing	Variant summary: ALOX12B c.1859C>A (p.Pro620Gln) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251462 control chromosomes (gnomAD). c.1859C>A has been reported in the literature in individuals affected with Ichthyosis in the homozygous and compound heterozygous state (Hotz_2021, Gorukmez_2023). These data indicate that the variant may be associated with disease. In one patient heterozygous with the variant, a co-occurrence with a pathogenic variant in a different gene with a dominant inheritance pattern was reported (KRT1 c.1757dup, p.Tyr587fs; Frommhertz_2021), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33435499, 34273205, 36964972). ClinVar contains an entry for this variant (Variation ID: 374101). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Institute for Human Genetics, University Medical Center Freiburg	RCV001289513	SCV001477387	pathogenic	Autosomal recessive congenital ichthyosis 2	2021-01-07	no assertion criteria provided	clinical testing