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NM_003924.4(PHOX2B):c.466C>T (p.Gln156Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 9, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002335143.2

Allele description [Variation Report for NM_003924.4(PHOX2B):c.466C>T (p.Gln156Ter)]

NM_003924.4(PHOX2B):c.466C>T (p.Gln156Ter)

Gene:
PHOX2B:paired like homeobox 2B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p13
Genomic location:
Preferred name:
NM_003924.4(PHOX2B):c.466C>T (p.Gln156Ter)
HGVS:
  • NC_000004.12:g.41746286G>A
  • NG_008243.1:g.7685C>T
  • NM_003924.4:c.466C>TMANE SELECT
  • NP_003915.2:p.Gln156Ter
  • NP_003915.2:p.Gln156Ter
  • LRG_513t1:c.466C>T
  • LRG_513:g.7685C>T
  • LRG_513p1:p.Gln156Ter
  • NC_000004.11:g.41748303G>A
  • NM_003924.3:c.466C>T
Protein change:
Q156*
Molecular consequence:
  • NM_003924.4:c.466C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002638121Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 9, 2019) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV002638121.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.Q156* pathogenic mutation (also known as c.466C>T), located in coding exon 3 of the PHOX2B gene, results from a C to T substitution at nucleotide position 466. This changes the amino acid from a glutamine to a stop codon within coding exon 3. This frameshift occurs at the 3' terminus of PHOX2B and is not expected to trigger nonsense-mediated mRNA decay, but results in the loss of the polyalanine tract of the PHOX2B protein. In addition, other variants that result in the loss of the polyalanine tract (c.722_759del38 and c.691_698dupGGCCCGGG) have been reported in individuals with congenital central hypoventilation, Hirschsprung disease, and/or neuroblastoma (Trochet D et al. Am. J. Hum. Genet., 2005 Mar;76:421-6; Raabe EH et al. Oncogene, 2008 Jan;27:469-76; Low KJ et al. Pediatr. Pulmonol., 2014 Oct;49:E140-3; Mehta VJ et al. J Neuroophthalmol, 2016 Dec;36:414-416; Byers HM et al. Am. J. Med. Genet. A, 2018 06;176:1398-1404). As such, thep.Q156* alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024