rs1553820520
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_006218.4(PIK3CA):c.560A>C(p.Lys187Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000779 in 1,411,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. K187E) has been classified as Uncertain significance.
Frequency
Consequence
NM_006218.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3CA | NM_006218.4 | c.560A>C | p.Lys187Thr | missense_variant, splice_region_variant | 3/21 | ENST00000263967.4 | |
PIK3CA | XM_006713658.5 | c.560A>C | p.Lys187Thr | missense_variant, splice_region_variant | 3/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3CA | ENST00000263967.4 | c.560A>C | p.Lys187Thr | missense_variant, splice_region_variant | 3/21 | 2 | NM_006218.4 | P1 | |
PIK3CA | ENST00000643187.1 | c.560A>C | p.Lys187Thr | missense_variant, splice_region_variant | 3/22 | ||||
PIK3CA | ENST00000675467.1 | n.3367A>C | splice_region_variant, non_coding_transcript_exon_variant | 2/20 | |||||
PIK3CA | ENST00000675786.1 | c.560A>C | p.Lys187Thr | missense_variant, splice_region_variant, NMD_transcript_variant | 3/21 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000779 AC: 11AN: 1411462Hom.: 0 Cov.: 24 AF XY: 0.00000709 AC XY: 5AN XY: 705486
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2023 | The p.K187T variant (also known as c.560A>C), located in coding exon 2 of the PIK3CA gene, results from an A to C substitution at nucleotide position 560. The lysine at codon 187 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Cowden syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 06, 2018 | This sequence change replaces lysine with threonine at codon 187 of the PIK3CA protein (p.Lys187Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PIK3CA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at