ClinVar Miner

Submissions for variant NM_000096.3(CP):c.2684G>C (p.Gly895Ala) (rs139633388)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000419016 SCV000511090 uncertain significance not provided 2016-09-13 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000034882 SCV000734248 uncertain significance Deficiency of ferroxidase no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000419016 SCV000344153 uncertain significance not provided 2016-08-09 criteria provided, single submitter clinical testing
Fulgent Genetics RCV000034882 SCV000895541 uncertain significance Deficiency of ferroxidase 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000419016 SCV000564912 uncertain significance not provided 2018-05-31 criteria provided, single submitter clinical testing The G895A variant in the CP gene has been reported previously, as G876A due to alternate nomenclature, within a cohort of individuals with aceruloplasminemia (Kono et al., 2006); however, no additional phenotypic details or segregation information was provided. The G895A variant is observed in 407/276068 (0.147%) alleles in large population cohorts, with no homozygotes observed (Lek et al., 2016). The G895A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret G895A as a variant of uncertain significance.
GeneReviews RCV000034882 SCV000058488 pathologic Deficiency of ferroxidase 2013-04-18 no assertion criteria provided curation Converted during submission to Pathogenic.
Genetic Services Laboratory, University of Chicago RCV000334692 SCV000150893 uncertain significance not specified 2016-03-04 criteria provided, single submitter clinical testing
Invitae RCV000034882 SCV000760127 uncertain significance Deficiency of ferroxidase 2018-05-09 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 895 of the CP protein (p.Gly895Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs139633388, ExAC 0.2%). This variant has been reported in an individual affected with aceruloplasminemia (PMID: 16629161). ClinVar contains an entry for this variant (Variation ID: 42054). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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