ClinVar Miner

Submissions for variant NM_003924.4(PHOX2B):c.762A>C (p.Ala254=) (rs17884724)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000151648 SCV000199900 benign not specified 2015-10-12 criteria provided, single submitter clinical testing p.Ala254Ala in exon 3 of PHOX2B: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.4% (12/2634), i ncluding 1 homozygote, of East Asian chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs17884724).
Invitae RCV000231595 SCV000288034 benign Congenital central hypoventilation 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000151648 SCV000309892 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000231595 SCV000449534 benign Congenital central hypoventilation 2018-03-06 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.
GeneDx RCV000151648 SCV000518977 benign not specified 2016-05-20 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.
Ambry Genetics RCV000575949 SCV000664971 benign Hereditary cancer-predisposing syndrome 2016-11-23 criteria provided, single submitter clinical testing No disease association in small case-control study;Other data supporting benign classification
Integrated Genetics/Laboratory Corporation of America RCV000587434 SCV000698220 benign not provided 2016-08-31 criteria provided, single submitter clinical testing Variant summary: The c.762A>C (p.Ala254=) in PHOX2B gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC and 1000Gs at frequency of 0.026(300/11564 chrs tested), including numerous homozygous occurrences. This frequency exceeds the maximal expected frequency of a pathogenic allele (0.0000008) in this gene. The variant of interest was cited as Benign/Polymorphism by reputable database/clinical laboratories/published reports. It is widely accepted as a polymorphism in the field. Taking together, the variant was classified as Benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000151648 SCV000703659 benign not specified 2016-11-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001145119 SCV001305760 benign Neuroblastoma 2 2018-03-06 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.

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.