NM_003924.4(PHOX2B):c.814G>A (p.Gly272Ser) AND Haddad syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 18, 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:: RCV002231825.14

Allele description [Variation Report for NM_003924.4(PHOX2B):c.814G>A (p.Gly272Ser)]

NM_003924.4(PHOX2B):c.814G>A (p.Gly272Ser)

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.814G>A (p.Gly272Ser)

HGVS:

NC_000004.12:g.41745938C>T
NG_008243.1:g.8033G>A
NG_053075.1:g.64C>T
NM_003924.4:c.814G>AMANE SELECT
NP_003915.2:p.Gly272Ser
NP_003915.2:p.Gly272Ser
LRG_513t1:c.814G>A
LRG_513:g.8033G>A
LRG_513p1:p.Gly272Ser
NC_000004.11:g.41747955C>T
NM_003924.3:c.814G>A

Protein change:

G272S

Links:

dbSNP: rs1232625512

NCBI 1000 Genomes Browser:

rs1232625512

Molecular consequence:

NM_003924.4:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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solute carrier family 25 member 44 isoform b [Mus musculus]
solute carrier family 25 member 44 isoform b [Mus musculus]
gi|529250135|ref|NP_001268724.1|

Protein
Mus musculus leucine-rich repeat transmembrane neuronal 2 protein mRNA, complete...
Mus musculus leucine-rich repeat transmembrane neuronal 2 protein mRNA, complete cds
gi|29542686|gb|AY182027.1|

Nucleotide
Ctenitis nigrovenia (3)
Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000644056	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 18, 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

SCV000644056

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 18, 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, SCV000644056.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 467750). This variant has not been reported in the literature in individuals affected with PHOX2B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 272 of the PHOX2B protein (p.Gly272Ser).

#	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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