rs121913282

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5

The NM_006218.4(PIK3CA):​c.2102A>C​(p.His701Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. H701Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PIK3CA
NM_006218.4 missense

Scores

5
6
8

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.95
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PIK3CA. . Gene score misZ 5.5986 (greater than the threshold 3.09). Trascript score misZ 6.1406 (greater than threshold 3.09). GenCC has associacion of gene with hereditary breast carcinoma, vascular malformation, Cowden disease, Cowden syndrome 5, CLOVES syndrome, familial ovarian cancer, megalencephaly-capillary malformation-polymicrogyria syndrome, overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.754
PP5
Variant 3-179221072-A-C is Pathogenic according to our data. Variant chr3-179221072-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376052.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIK3CANM_006218.4 linkuse as main transcriptc.2102A>C p.His701Pro missense_variant 14/21 ENST00000263967.4
PIK3CAXM_006713658.5 linkuse as main transcriptc.2102A>C p.His701Pro missense_variant 14/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIK3CAENST00000263967.4 linkuse as main transcriptc.2102A>C p.His701Pro missense_variant 14/212 NM_006218.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Breast neoplasm Pathogenic:1
Likely pathogenic, no assertion criteria providedliterature onlyDatabase of Curated Mutations (DoCM)Jul 14, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.69
D;.
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.052
D
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
0.82
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.1
N;.
REVEL
Uncertain
0.40
Sift
Benign
0.27
T;.
Sift4G
Benign
0.29
T;.
Polyphen
0.76
P;.
Vest4
0.84
MutPred
0.75
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP
0.89
MPC
2.6
ClinPred
0.63
D
GERP RS
5.4
Varity_R
0.82
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121913282; hg19: chr3-178938860; COSMIC: COSV55886031; API