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Insufficiently evaluated pathogenic
(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)
Summary of published research, and additional commentary
dbSNP reports that this variant has 5% allele frequency in a 120 chromosome low-coverage CEU panel (1000 genomes) and 2.6% in a mixed panel of Caucasian & African American samples. Lorenz-Depiereux et al. point to this as suggesting that the variant is a non-pathogenic polymorphism.
The predicted incidence of homozygotes (1 in 400) vs. the incidence of the disease (quite rare) implies that this variant is not causal.
Added in this revision:
Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A, Höhne W, Schauer G, Lehmann
M, Roscioli T, Schnabel D, Epplen JT, Knisely A, Superti-Furga A, McGill J,
Filippone M, Sinaiko AR, Vallance H, Hinrichs B, Smith W, Ferre M, Terkeltaub R,
Nürnberg P. Mutations in ENPP1 are associated with 'idiopathic' infantile
arterial calcification. Nat Genet. 2003 Aug;34(4):379-81. PubMed PMID: 12881724.
Lorenz-Depiereux B, Schnabel D, Tiosano D, Häusler G, Strom TM.
Loss-of-function ENPP1 mutations cause both generalized arterial calcification of
infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet. 2010
Feb 12;86(2):267-72. Epub 2010 Feb 4. PubMed PMID: 20137773; PubMed Central
The footnote to Table 3 states: “The mutation reported in this paper (c.2320C>T [p.Arg774Cys]) has since been shown to be a polymorphism (rs28933977) with a minor allele frequency of 5%.”