NM_003924.4(PHOX2B):c.765_779dup (p.Ala256_Ala260dup) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 2022
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:: RCV002395193.2

Allele description [Variation Report for NM_003924.4(PHOX2B):c.765_779dup (p.Ala256_Ala260dup)]

NM_003924.4(PHOX2B):c.765_779dup (p.Ala256_Ala260dup)

Gene:

PHOX2B:paired like homeobox 2B [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

4p13

Genomic location:

Preferred name:

NM_003924.4(PHOX2B):c.765_779dup (p.Ala256_Ala260dup)

HGVS:

NC_000004.12:g.41745984_41745998dup
NG_008243.1:g.7984_7998dup
NG_053075.1:g.110_124dup
NM_003924.3:c.765_779dup15
NM_003924.4:c.765_779dupMANE SELECT
NP_003915.2:p.Ala256_Ala260dup
NP_003915.2:p.Ala256_Ala260dup
LRG_513t1:c.765_779dup
LRG_513:g.7984_7998dup
LRG_513p1:p.Ala256_Ala260dup
NC_000004.11:g.41748001_41748015dup
NM_003924.3:c.765_779dup
NM_003924.3:c.765_779dup15
NM_003924.3:c.765_779dupGGCAGCGGCGGCAGC

Links:

dbSNP: rs761018157

NCBI 1000 Genomes Browser:

rs761018157

Molecular consequence:

NM_003924.4:c.765_779dup - inframe_insertion - [Sequence Ontology: SO:0001821]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002670717	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 23, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12640453, 15121777, 20456320, 32573669 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002670717

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 23, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome.

Amiel J, Laudier B, Attié-Bitach T, Trang H, de Pontual L, Gener B, Trochet D, Etchevers H, Ray P, Simonneau M, Vekemans M, Munnich A, Gaultier C, Lyonnet S.

Nat Genet. 2003 Apr;33(4):459-61. Epub 2003 Mar 17.

PubMed [citation]

PMID:: 12640453

PHOX2B mutations and polyalanine expansions correlate with the severity of the respiratory phenotype and associated symptoms in both congenital and late onset Central Hypoventilation syndrome.

Matera I, Bachetti T, Puppo F, Di Duca M, Morandi F, Casiraghi GM, Cilio MR, Hennekam R, Hofstra R, Schöber JG, Ravazzolo R, Ottonello G, Ceccherini I.

J Med Genet. 2004 May;41(5):373-80. No abstract available.

PubMed [citation]

PMID:: 15121777
PMCID:: PMC1735781

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002670717.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.Ala241[25] pathogenic mutation, located in coding exon 3 of the PHOX2B gene, results from an expansion of the polyalanine repeat region from 20 to 25 repeats. This expansion mutation is associated with congenital central hypoventilation syndrome (Amiel J et al. Nat. Genet., 2003 Apr;33(4):459-61; Matera I et al. J. Med. Genet., 2004 May;41(5):373-80; Serra A et al. Ann. Hum. Genet., 2010 Jul;74(4):369-74; Australian Genomics Health Alliance Acute Care Flagship. JAMA 2020 06;323(24):2503-11). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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