NM_003924.4(PHOX2B):c.811_847del (p.Gln271fs) AND Haddad syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 10, 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:: RCV001319416.5

Allele description [Variation Report for NM_003924.4(PHOX2B):c.811_847del (p.Gln271fs)]

NM_003924.4(PHOX2B):c.811_847del (p.Gln271fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

4p13

Genomic location:

Preferred name:

NM_003924.4(PHOX2B):c.811_847del (p.Gln271fs)

HGVS:

NC_000004.12:g.41745906_41745942del
NG_008243.1:g.8030_8066del
NG_053075.1:g.32_68del
NM_003924.3:c.811_847del37
NM_003924.4:c.811_847delMANE SELECT
NP_003915.2:p.Gln271fs
LRG_513t1:c.811_847del37
LRG_513:g.8030_8066del
NC_000004.11:g.41747922_41747958del
NC_000004.11:g.41747923_41747959del

Protein change:

Q271fs

Links:

dbSNP: rs1733869585

NCBI 1000 Genomes Browser:

rs1733869585

Molecular consequence:

NM_003924.4:c.811_847del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Haddad syndrome (OHD)
Synonyms:: Ondine-Hirschsprung disease
Identifiers:: MONDO: MONDO:0020493; MedGen: C1859049; Orphanet: 99803

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001510158	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 10, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001510158

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 10, 2023)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001510158.4

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

Description

This sequence change creates a premature translational stop signal (p.Gln271Serfs*26) in the PHOX2B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the PHOX2B protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PHOX2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1019912). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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