ClinVar Miner

Submissions for variant NM_003924.4(PHOX2B):c.552C>T (p.Ser184=) (rs17885216)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000214751 SCV000269642 benign not specified 2016-01-29 criteria provided, single submitter clinical testing p.Ser184Ser 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 1.2% (765/66160) of European chromosomes, including 1 homozygote by the Exome Aggregation Consort ium (ExAC, http://exac.broadinstitute.org; dbSNP rs17885216).
Invitae RCV000232548 SCV000288023 benign Congenital central hypoventilation 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000214751 SCV000309886 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000232548 SCV000449543 benign Congenital central hypoventilation 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.
Illumina Clinical Services Laboratory,Illumina RCV000291806 SCV000449544 benign Neuroblastoma 2 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.
GeneDx RCV000214751 SCV000521682 benign not specified 2017-11-30 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.
Integrated Genetics/Laboratory Corporation of America RCV000590390 SCV000698219 benign not provided 2016-05-17 criteria provided, single submitter clinical testing Variant summary: The PHOX2B c.552C>T (p.Ser184Ser) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may create a novel ESE site of SF2/ASF. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1028/120536 control chromosomes (4 homozygotes) at a frequency of 0.0085286, which is approximately 10234 times the estimated maximal expected allele frequency of a pathogenic PHOX2B variant (0.0000008), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000214751 SCV001157021 benign not specified 2018-09-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001024232 SCV001186214 benign Hereditary cancer-predisposing syndrome 2018-06-20 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign

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