NM_004387.4(NKX2-5):c.147_163delinsGCCTCCT (p.Ala50fs) AND Atrial septal defect 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 22, 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:: RCV000690794.3

Allele description [Variation Report for NM_004387.4(NKX2-5):c.147_163delinsGCCTCCT (p.Ala50fs)]

NM_004387.4(NKX2-5):c.147_163delinsGCCTCCT (p.Ala50fs)

Gene:

NKX2-5:NK2 homeobox 5 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

5q35.1

Genomic location:

Preferred name:

NM_004387.4(NKX2-5):c.147_163delinsGCCTCCT (p.Ala50fs)

HGVS:

NC_000005.10:g.173234921_173234937delinsAGGAGGC
NG_013340.1:g.5376_5392delinsGCCTCCT
NM_001166175.2:c.147_163delinsGCCTCCT
NM_001166176.2:c.147_163delinsGCCTCCT
NM_004387.4:c.147_163delinsGCCTCCTMANE SELECT
NP_001159647.1:p.Ala50fs
NP_001159648.1:p.Ala50fs
NP_004378.1:p.Ala50fs
LRG_671t1:c.147_163delinsGCCTCCT
LRG_671:g.5376_5392delinsGCCTCCT
LRG_671p1:p.Ala50fs
NC_000005.9:g.172661924_172661940delinsAGGAGGC

Protein change:

A50fs

Links:

dbSNP: rs1561621507

NCBI 1000 Genomes Browser:

rs1561621507

Molecular consequence:

NM_001166175.2:c.147_163delinsGCCTCCT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001166176.2:c.147_163delinsGCCTCCT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004387.4:c.147_163delinsGCCTCCT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Atrial septal defect 7
Synonyms:: Atrial septal defect with atrioventricular conduction defects; ASD WITH OR WITHOUT ATRIOVENTRICULAR CONDUCTION DEFECTS; Atrial septal defect 7 with or without atrioventricular conduction defects; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007173; MedGen: C3276096; Orphanet: 1479; OMIM: 108900

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PREDICTED: Homo sapiens sprouty related EVH1 domain containing 1 (SPRED1), trans...
PREDICTED: Homo sapiens sprouty related EVH1 domain containing 1 (SPRED1), transcript variant X2, mRNA
gi|2462542950|ref|XM_054377382.1|

Nucleotide
PMC Links for Gene (Select 161742) (46)
PMC
sprouty-related, EVH1 domain-containing protein 1 isoform X2 [Homo sapiens]
sprouty-related, EVH1 domain-containing protein 1 isoform X2 [Homo sapiens]
gi|2217300267|ref|XP_047288157.1|

Protein
DDX3X[gene] (887)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000818521	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 22, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21561848, 9651244, 10948187, 15689439, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000818521

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 22, 2018)

germline

clinical testing

PubMed (5)
[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

Sequence variations of NKX2-5 and HAND1 genes in patients with atrial isomerism.

Hatemi AC, Güleç C, Cine N, Vural B, Hatırnaz O, Sayitoğlu M, Oztunç F, Saltık L, Kansız E, Erginel Ünaltuna N.

Anadolu Kardiyol Derg. 2011 Jun;11(4):319-28. doi: 10.5152/akd.2011.083. Epub 2011 May 11.

PubMed [citation]

PMID:: 21561848

Congenital heart disease caused by mutations in the transcription factor NKX2-5.

Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, Seidman JG.

Science. 1998 Jul 3;281(5373):108-11.

PubMed [citation]

PMID:: 9651244

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000818521.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change results in a premature translational stop signal in the NKX2-5 gene (p.Ala50Profs*126). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 275 amino acids of the NKX2-5 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NKX2-5-related disease. Two different truncations (p.Gln170*, p.Leu202Argfs*49) that lie downstream of this variant have been determined to be pathogenic and likely pathogenic respectively (PMID: 21561848, 9651244, 10948187, 15689439). This suggests that deletion of this region of the NKX2-5 protein is causative of disease. 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 14, 2024

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