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

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 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:: RCV003716268.1

Allele description

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

Genes:

NKX2-1:NK2 homeobox 1 [Gene - OMIM - HGNC]
SFTA3:surfactant associated 3 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

14q13.3

Genomic location:

Preferred name:

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

HGVS:

NC_000014.9:g.36517956dup
NG_013365.1:g.7274dup
NG_128910.1:g.566dup
NM_001079668.3:c.532dupMANE SELECT
NM_003317.4:c.442dup
NP_001073136.1:p.Asp178fs
NP_003308.1:p.Asp148fs
NC_000014.8:g.36987156_36987157insC
NC_000014.8:g.36987161dup

Protein change:

D148fs

Molecular consequence:

NM_001079668.3:c.532dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003317.4:c.442dup - 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
SCV004501608	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 23, 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

SCV004501608

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 23, 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 Invitae, SCV004501608.1

#	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 results in a frameshift in the NKX2-1 gene (p.Asp178Glyfs*261). 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 and extend the protein by 36 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NKX2-1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the NKX2-1 protein in which other variant(s) (p.Gln356*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Feb 28, 2024

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