ClinVar

Description

Variant summary: The variant involves the deletion of exons 23-29 in the ABCC6 gene. A presumed nomenclature of c.(2995+1_2996-1)_(4208+1_4209-1)del has been designated for the purposes of this classification. This Copy Number Variant (CNV) is expected to alter the reading frame and predicted to result in a truncation or absence of the encoded protein due to nonsense mediated decay (NMD). This variant was detected at a frequency of 0.00074 in 125176 control chromosomes in the gnomAD database (Structural Variants v4.0 dataset), and was found predominantly in the European subpopulation at a frequency of 0.0012. The variant, described as exon 23-29 deletion, has been reported in the as one of the most frequent variants found in individuals affected with Pseudoxanthoma Elasticum (e.g. LeSaux_2001, Bartstra_2021). 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: 11536079, 33812167). ClinVar contains several entries for similar variants (e.g. Variation IDs: 688963, 3063406, 6573). Based on the evidence outlined above, the variant was classified as pathogenic.