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NM_003924.4(PHOX2B):c.729_749del (p.Ala254_Ala260del) AND Haddad syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 1, 2018
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:
RCV003103842.12

Allele description [Variation Report for NM_003924.4(PHOX2B):c.729_749del (p.Ala254_Ala260del)]

NM_003924.4(PHOX2B):c.729_749del (p.Ala254_Ala260del)

Genes:
PHOX2B:paired like homeobox 2B [Gene - OMIM - HGNC]
LOC110011216:paired like homeobox 2b polyalanine repeat instability region [Gene]
Variant type:
Deletion
Cytogenetic location:
4p13
Genomic location:
Preferred name:
NM_003924.4(PHOX2B):c.729_749del (p.Ala254_Ala260del)
HGVS:
  • NC_000004.12:g.41746008_41746028del
  • NG_008243.1:g.7948_7968del
  • NG_053075.1:g.134_154del
  • NM_003924.3:c.729_749del21
  • NM_003924.4:c.729_749delMANE SELECT
  • NP_003915.2:p.Ala254_Ala260del
  • LRG_513t1:c.729_749del21
  • LRG_513:g.7948_7968del
  • NC_000004.11:g.41748020_41748040del
  • NC_000004.11:g.41748025_41748045del
  • NM_003924.3:c.729_749delAGCGGCGGCGGCCGCGGCAGC
Links:
dbSNP: rs772448418
NCBI 1000 Genomes Browser:
rs772448418
Molecular consequence:
  • NM_003924.4:c.729_749del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000947726Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 1, 2018) 		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

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, SCV000947726.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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. This variant, c.729_749del, results in the deletion of 7 amino acids of the PHOX2B protein (p.Ala254_Ala260del), but otherwise preserves the integrity of the reading frame. While this variant is present in population databases (rs772448418), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PHOX2B-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown.

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

Last Updated: Nov 3, 2024