NM_001079668.3(NKX2-1):c.532del (p.Asp178fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 6, 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:: RCV001946886.6

Allele description [Variation Report for NM_001079668.3(NKX2-1):c.532del (p.Asp178fs)]

NM_001079668.3(NKX2-1):c.532del (p.Asp178fs)

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.532del (p.Asp178fs)

HGVS:

NC_000014.9:g.36517956del
NG_013365.1:g.7274del
NM_001079668.3:c.532delMANE SELECT
NM_003317.4:c.442del
NP_001073136.1:p.Asp178fs
NP_003308.1:p.Asp148fs
NC_000014.8:g.36987157del
NC_000014.8:g.36987161del

Protein change:

D148fs

Links:

dbSNP: rs2139408039

NCBI 1000 Genomes Browser:

rs2139408039

Molecular consequence:

NM_001079668.3:c.532del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003317.4:c.442del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002245525	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 6, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16220345, 24129101, 24714694, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002245525

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 6, 2022)

germline

clinical testing

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

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

Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea.

Costa MC, Costa C, Silva AP, Evangelista P, Santos L, Ferro A, Sequeiros J, Maciel P.

Neurogenetics. 2005 Dec;6(4):209-15. Epub 2005 Oct 12.

PubMed [citation]

PMID:: 16220345

NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients.

Shetty VB, Kiraly-Borri C, Lamont P, Bikker H, Choong CS.

J Pediatr Endocrinol Metab. 2014 Mar;27(3-4):373-8. doi: 10.1515/jpem-2013-0109.

PubMed [citation]

PMID:: 24129101

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002245525.3

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

Description

ClinVar contains an entry for this variant (Variation ID: 1456475). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NKX2-1 protein in which other variant(s) (p.Gln249*) have been determined to be pathogenic (PMID: 16220345, 24129101, 24714694). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with NKX2-1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp178Thrfs*2) in the NKX2-1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 224 amino acid(s) of the NKX2-1 protein.

#	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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