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NM_003924.4(PHOX2B):c.722_759del (p.Ala241fs) AND PHOX2B-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 14, 2023
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:
RCV003415666.4

Allele description [Variation Report for NM_003924.4(PHOX2B):c.722_759del (p.Ala241fs)]

NM_003924.4(PHOX2B):c.722_759del (p.Ala241fs)

Genes:
LOC110011216:paired like homeobox 2b polyalanine repeat instability region [Gene]
PHOX2B:paired like homeobox 2B [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
4p13
Genomic location:
Preferred name:
NM_003924.4(PHOX2B):c.722_759del (p.Ala241fs)
HGVS:
  • NC_000004.12:g.41746000_41746037del
  • NG_008243.1:g.7941_7978del
  • NG_053075.1:g.126_163del
  • NM_003924.3:c.722_759del
  • NM_003924.4:c.722_759delMANE SELECT
  • NP_003915.2:p.Ala241fs
  • LRG_513t1:c.722_759del
  • LRG_513:g.7941_7978del
  • NC_000004.11:g.41748017_41748054del
  • NM_003924.3:c.722_759del38
Note:
NCBI staff established an HGVS expression for this deletion based on the trace in Figure 1 of the paper by Amiel et al., 2003 (PubMed 12640453).
Protein change:
A241fs
Links:
OMIM: 603851.0003; dbSNP: rs1733878065
NCBI 1000 Genomes Browser:
rs1733878065
Molecular consequence:
  • NM_003924.4:c.722_759del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
PHOX2B-related disorder
Synonyms:
PHOX2B-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004117842PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 14, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004117842.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The PHOX2B c.722_759del38 variant is predicted to result in a frameshift and premature protein termination (p.Ala241Glyfs*106). This variant has previously been reported to be causative for congenital central hypoventilation syndrome (CCHS) and tumors of the sympathetic nervous system (Amiel et al. 2003. PubMed ID: 12640453; Trochet et al. 2005. PubMed ID: 16249188; Trochet et al. 2009. PubMed ID: 19058226; Di Lascio et al. 2018. PubMed ID: 29098737). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), and is interpreted as Pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/6010/). Frameshift variants in PHOX2B are expected to be pathogenic. This variant is interpreted as pathogenic.

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

Last Updated: May 19, 2024