Submissions for variant NM_003924.4(PHOX2B):c.234C>T (p.Tyr78=)

gnomAD frequency: 0.00361  dbSNP: rs73810366

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001507144	SCV000288021	benign	Haddad syndrome	2024-01-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000250345	SCV000309883	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000573371	SCV000674207	benign	Hereditary cancer-predisposing syndrome	2017-02-13	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590552	SCV000698216	benign	not provided	2016-05-17	criteria provided, single submitter	clinical testing	Variant summary: The PHOX2B c.234C>T (p.Tyr78Tyr) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. MutationTaster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict the variant not to affect normal splicing. This variant was found in 114/120758 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0101498 (103/10148). This frequency is about 12180 times the estimated maximal expected allele frequency of a pathogenic PHOX2B variant (0.0000008), highly suggesting this is a benign polymorphism found primarily in the populations of African origin. Taken together, this variant is classified as Benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000250345	SCV000711341	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Tyr78Tyr in exon 1 of PHOX2B: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.1% (49/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs73810366).
GeneDx	RCV000250345	SCV000718380	likely benign	not specified	2017-11-24	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.
Illumina Laboratory Services, Illumina	RCV001149517	SCV001310473	benign	Neuroblastoma, susceptibility to, 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.
Illumina Laboratory Services, Illumina	RCV001080799	SCV001310474	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.
Sema4, Sema4	RCV000573371	SCV002535393	benign	Hereditary cancer-predisposing syndrome	2021-02-24	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001149517	SCV004016557	benign	Neuroblastoma, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000250345	SCV003839830	benign	not specified	2022-07-28	no assertion criteria provided	clinical testing