NM_001079668.3(NKX2-1):c.278_306del (p.Ala93fs) AND Choreoathetosis, hypothyroidism, and neonatal respiratory distress

Clinical significance:Pathogenic (Last evaluated: Jan 10, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001200886.1

Allele description [Variation Report for NM_001079668.3(NKX2-1):c.278_306del (p.Ala93fs)]

NM_001079668.3(NKX2-1):c.278_306del (p.Ala93fs)

Genes:
NKX2-1:NK2 homeobox 1 [Gene - OMIM - HGNC]
SFTA3:surfactant associated 3 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
14q13.3
Genomic location:
Preferred name:
NM_001079668.3(NKX2-1):c.278_306del (p.Ala93fs)
HGVS:
  • NC_000014.9:g.36519148_36519176del
  • NG_013365.1:g.6056_6084del
  • NM_001079668.3:c.278_306delMANE SELECT
  • NM_003317.4:c.188_216del
  • NP_001073136.1:p.Ala93fs
  • NP_003308.1:p.Ala63fs
  • NC_000014.8:g.36988353_36988381del
  • NM_001079668.2:c.278_306del
Protein change:
A63fs
Molecular consequence:
  • NM_001079668.3:c.278_306del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003317.4:c.188_216del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Choreoathetosis, hypothyroidism, and neonatal respiratory distress (CAHTP)
Synonyms:
BRAIN-LUNG-THYROID SYNDROME; CHOREOATHETOSIS AND CONGENITAL HYPOTHYROIDISM WITH PULMONARY DYSFUNCTION
Identifiers:
MONDO: MONDO:0012593; MedGen: C1970269; Orphanet: 209905; OMIM: 610978

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001371791Johns Hopkins Genomics, Johns Hopkins Universitycriteria provided, single submitter
Pathogenic
(Jan 10, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Physical and functional interactions between homeodomain NKX2.1 and winged helix/forkhead FOXA1 in lung epithelial cells.

Minoo P, Hu L, Xing Y, Zhu NL, Chen H, Li M, Borok Z, Li C.

Mol Cell Biol. 2007 Mar;27(6):2155-65. Epub 2007 Jan 12.

PubMed [citation]
PMID:
17220277
PMCID:
PMC1820505

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 Johns Hopkins Genomics, Johns Hopkins University, SCV001371791.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This frameshift variant is predicted to lead to a new stop codon that is downstream of the native stop codon. The resulting transcript is not expected to undergo nonsense-mediated decay and likely results in an extended protein product (335 novel C-terminal amino acids replacing the last 308 amino acids of NKX2-1). This novel protein is predicted to lack the NKX2-1 homeodomain, a highly conserved DNA binding motif that is essential for the function of NKX2-1. NKX2-1 c.278_306del has been reported in an individual with chorea. This variant is absent from a large population dataset. We consider this variant to be pathogenic.

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

Last Updated: Feb 27, 2021

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