chr5-173232820-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004387.4(NKX2-5):c.724G>A(p.Gly242Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G242R) has been classified as Uncertain significance.
Frequency
Consequence
NM_004387.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-5 | NM_004387.4 | c.724G>A | p.Gly242Ser | missense_variant | 2/2 | ENST00000329198.5 | |
NKX2-5 | NM_001166175.2 | c.*677G>A | 3_prime_UTR_variant | 2/2 | |||
NKX2-5 | NM_001166176.2 | c.*523G>A | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-5 | ENST00000329198.5 | c.724G>A | p.Gly242Ser | missense_variant | 2/2 | 1 | NM_004387.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459596Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 726040
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Atrial septal defect 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 07, 2019 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NKX2-5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 242 of the NKX2-5 protein (p.Gly242Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 22, 2023 | The p.G242S variant (also known as c.724G>A), located in coding exon 2 of the NKX2-5 gene, results from a G to A substitution at nucleotide position 724. The glycine at codon 242 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at