ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.2364G>A (p.Val788=) (rs2274515)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078572 SCV000110428 benign not specified 2013-07-30 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078572 SCV000303464 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000364141 SCV000463345 benign Peroxisome biogenesis disorder 4a (zellweger) 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Integrated Genetics/Laboratory Corporation of America RCV000078572 SCV000917989 benign not specified 2018-04-06 criteria provided, single submitter clinical testing Variant summary: Variant c.2364G>A (p.Val788Val) affects a non-conserved neucleotide resulting a synonymous change in the ATPase, AAA-type, core domain of the encoded protein. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.086 in 276948 control chromosomes in the gnomAD database, including 1712 homozygotes. The observed variant frequency is approximately 44.65 fold of the estimated maximal expected allele frequency for a pathogenic variant in PEX6 causing Zellweger Syndrome phenotype (0.0019), strongly suggesting that the variant is benign. c.2364G>A has been reported in the literature in individuals affected with Zellweger Syndrome and authors listed variant as SNP and neutral (Yik_2009). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar and classified the variant as benign (2 labs)/likely benign (1 lab). Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000676092 SCV000973687 benign not provided 2018-06-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000676092 SCV000801830 benign not provided 2015-10-23 no assertion criteria provided 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.