rs587782930
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004387.4(NKX2-5):c.721_728del(p.Tyr241GlyfsTer8) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y241Y) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
NKX2-5
NM_004387.4 frameshift
NM_004387.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.94
Genes affected
NKX2-5 (HGNC:2488): (NK2 homeobox 5) This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 46 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-173232815-CACGCCGTA-C is Pathogenic according to our data. Variant chr5-173232815-CACGCCGTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 156160.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-173232815-CACGCCGTA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-5 | NM_004387.4 | c.721_728del | p.Tyr241GlyfsTer8 | frameshift_variant | 2/2 | ENST00000329198.5 | |
NKX2-5 | NM_001166175.2 | c.*674_*681del | 3_prime_UTR_variant | 2/2 | |||
NKX2-5 | NM_001166176.2 | c.*520_*527del | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-5 | ENST00000329198.5 | c.721_728del | p.Tyr241GlyfsTer8 | frameshift_variant | 2/2 | 1 | NM_004387.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Atrial septal defect 7 Pathogenic:1
Pathogenic, no assertion criteria provided | research | Nemer Genomics and Translation Biomedicine Lab, American University of Beirut | Jan 01, 2014 | Sudden cardiac death risk with previously attributed Familial Atrial Septal defect Secundum type with progressive atrioventricular block - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at