ClinVar Miner

Submissions for variant NM_173076.3(ABCA12):c.4541G>A (p.Arg1514His)

gnomAD frequency: 0.00001  dbSNP: rs28940270
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003407261 SCV004112977 likely pathogenic ABCA12-related disorder 2022-10-24 criteria provided, single submitter clinical testing The ABCA12 c.4541G>A variant is predicted to result in the amino acid substitution p.Arg1514His. This variant was reported in the homozygous and compound heterozygous states in individuals with lamellar ichthyosis type 2 (Lefevre et al. 2003. PubMed ID: 12915478; Pigg et al. 2016. PubMed ID: 27025581). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-215846949-C-T). Taken together, this variant is interpreted as likely pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782003 SCV005394553 pathogenic Lamellar ichthyosis 2024-09-12 criteria provided, single submitter clinical testing Variant summary: ABCA12 c.4541G>A (p.Arg1514His) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of 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 251174 control chromosomes (gnomAD). c.4541G>A has been reported in the literature in multiple individuals affected with Lamellar Ichthyosis (Lefevre_2003, Hellstrm Pigg_2016, Hake__2021, Hotz_2023). These data indicate that the variant is very likely to be associated with disease. 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: 34908195, 27025581, 36980989, 12915478). ClinVar contains an entry for this variant (Variation ID: 2857). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000002991 SCV000023149 pathogenic Autosomal recessive congenital ichthyosis 4A 2003-09-15 no assertion criteria provided literature only

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