ClinVar Miner

Submissions for variant NM_001378615.1(CC2D2A):c.157G>A (p.Glu53Lys)

gnomAD frequency: 0.00005  dbSNP: rs373080748
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000331852 SCV000329210 uncertain significance not provided 2016-04-12 criteria provided, single submitter clinical testing The E53K variant in the CC2D2A gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The E53K variant was not observed with any significant frequency in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these population. The E53K variant is a non-conservative amino acid substitution which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret E53K as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001305618 SCV001494957 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 53 of the CC2D2A protein (p.Glu53Lys). This variant is present in population databases (rs373080748, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CC2D2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 279737). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CC2D2A protein function. 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.
Ambry Genetics RCV002518803 SCV003694028 uncertain significance Inborn genetic diseases 2022-10-26 criteria provided, single submitter clinical testing The c.157G>A (p.E53K) alteration is located in exon 5 (coding exon 3) of the CC2D2A gene. This alteration results from a G to A substitution at nucleotide position 157, causing the glutamic acid (E) at amino acid position 53 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005031842 SCV005660476 uncertain significance Meckel syndrome, type 6; Joubert syndrome 9; COACH syndrome 2; Retinitis pigmentosa 93 2024-03-06 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.