rs1057519928
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP2PP5
The NM_006218.4(PIK3CA):c.2177A>C(p.Glu726Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E726K) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 31)
Consequence
PIK3CA
NM_006218.4 missense
NM_006218.4 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 8.95
Genes affected
PIK3CA (HGNC:8975): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr3-179221146-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 376476.Status of the report is reviewed_by_expert_panel, 3 stars.
PP2
?
Missense variant where missense usually causes diseases, PIK3CA
PP5
?
Variant 3-179221147-A-C is Pathogenic according to our data. Variant chr3-179221147-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376477.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3CA | NM_006218.4 | c.2177A>C | p.Glu726Ala | missense_variant | 14/21 | ENST00000263967.4 | |
PIK3CA | XM_006713658.5 | c.2177A>C | p.Glu726Ala | missense_variant | 14/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3CA | ENST00000263967.4 | c.2177A>C | p.Glu726Ala | missense_variant | 14/21 | 2 | NM_006218.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:8
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Squamous cell lung carcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Breast neoplasm Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Lung adenocarcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Neoplasm of uterine cervix Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Transitional cell carcinoma of the bladder Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Brainstem glioma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Neoplasm of the large intestine Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Squamous cell carcinoma of the head and neck Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
P;.
Vest4
MutPred
Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at