chr11-17091408-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_002645.4(PIK3C2A):āc.4804C>Gā(p.Pro1602Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00025 ( 0 hom., cov: 32)
Exomes š: 0.00023 ( 0 hom. )
Consequence
PIK3C2A
NM_002645.4 missense
NM_002645.4 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 9.75
Genes affected
PIK3C2A (HGNC:8971): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00025 (38/152278) while in subpopulation NFE AF= 0.000397 (27/68018). AF 95% confidence interval is 0.00028. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3C2A | NM_002645.4 | c.4804C>G | p.Pro1602Ala | missense_variant | 32/33 | ENST00000691414.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3C2A | ENST00000691414.1 | c.4804C>G | p.Pro1602Ala | missense_variant | 32/33 | NM_002645.4 | P1 | ||
PIK3C2A | ENST00000265970.11 | c.4804C>G | p.Pro1602Ala | missense_variant | 31/32 | 1 | P1 | ||
PIK3C2A | ENST00000531428.1 | n.1326C>G | non_coding_transcript_exon_variant | 12/13 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000410 AC: 103AN: 251254Hom.: 0 AF XY: 0.000376 AC XY: 51AN XY: 135788
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GnomAD4 exome AF: 0.000228 AC: 333AN: 1461524Hom.: 0 Cov.: 31 AF XY: 0.000216 AC XY: 157AN XY: 727100
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GnomAD4 genome AF: 0.000250 AC: 38AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74450
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.4804C>G (p.P1602A) alteration is located in exon 31 (coding exon 31) of the PIK3C2A gene. This alteration results from a C to G substitution at nucleotide position 4804, causing the proline (P) at amino acid position 1602 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at