chr1-204431741-T-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001377334.1(PIK3C2B):c.4208A>T(p.Gln1403Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
PIK3C2B
NM_001377334.1 missense
NM_001377334.1 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.75
Genes affected
PIK3C2B (HGNC:8972): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta) 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 sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36566582).
BS2
?
High AC in GnomAd at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3C2B | NM_001377334.1 | c.4208A>T | p.Gln1403Leu | missense_variant | 28/33 | ENST00000684373.1 | |
PIK3C2B | NM_002646.4 | c.4208A>T | p.Gln1403Leu | missense_variant | 30/35 | ||
PIK3C2B | NM_001377335.1 | c.4124A>T | p.Gln1375Leu | missense_variant | 31/36 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3C2B | ENST00000684373.1 | c.4208A>T | p.Gln1403Leu | missense_variant | 28/33 | NM_001377334.1 | P1 | ||
PPP1R15B-AS1 | ENST00000443515.1 | n.147-3596T>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152198Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251494Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135922
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727240
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74360
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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 | Jan 03, 2024 | The c.4208A>T (p.Q1403L) alteration is located in exon 29 (coding exon 27) of the PIK3C2B gene. This alteration results from a A to T substitution at nucleotide position 4208, causing the glutamine (Q) at amino acid position 1403 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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