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rs61757718

chr12-18648027-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001288772.2(PIK3C2G):c.4460G>C(p.Ter1487SerextTer4) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,581,494 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 14 hom., cov: 32)
Exomes 𝑓: 0.016 ( 234 hom. )

Consequence

PIK3C2G
NM_001288772.2 stop_lost

Scores

1
2
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72
Variant links:
Genes affected
PIK3C2G (HGNC:8973): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma) 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. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_addAF=-0.480236).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-18648027-G-C is Benign according to our data. Variant chr12-18648027-G-C is described in Lovd as [Likely_benign].
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0115 (1749/151858) while in subpopulation NFE AF= 0.0191 (1298/67956). AF 95% confidence interval is 0.0182. There are 14 homozygotes in gnomad4. There are 794 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIK3C2GNM_001288772.2 linkuse as main transcriptc.4460G>C p.Ter1487SerextTer4 stop_lost 33/33 ENST00000538779.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIK3C2GENST00000538779.6 linkuse as main transcriptc.4460G>C p.Ter1487SerextTer4 stop_lost 33/335 NM_001288772.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0115
AC:
1751
AN:
151738
Hom.:
14
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00296
Gnomad AMI
AF:
0.0197
Gnomad AMR
AF:
0.00947
Gnomad ASJ
AF:
0.000578
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00684
Gnomad FIN
AF:
0.0105
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0191
Gnomad OTH
AF:
0.0101
GnomAD3 exomes
AF:
0.0110
AC:
2503
AN:
227776
Hom.:
13
AF XY:
0.0117
AC XY:
1443
AN XY:
123652
show subpopulations
Gnomad AFR exome
AF:
0.00201
Gnomad AMR exome
AF:
0.00510
Gnomad ASJ exome
AF:
0.00161
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00702
Gnomad FIN exome
AF:
0.0108
Gnomad NFE exome
AF:
0.0174
Gnomad OTH exome
AF:
0.0110
GnomAD4 exome
AF:
0.0162
AC:
23134
AN:
1429636
Hom.:
234
Cov.:
26
AF XY:
0.0161
AC XY:
11450
AN XY:
710982
show subpopulations
Gnomad4 AFR exome
AF:
0.00232
Gnomad4 AMR exome
AF:
0.00522
Gnomad4 ASJ exome
AF:
0.00146
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00774
Gnomad4 FIN exome
AF:
0.0108
Gnomad4 NFE exome
AF:
0.0190
Gnomad4 OTH exome
AF:
0.0130
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0115
AC:
1749
AN:
151858
Hom.:
14
Cov.:
32
AF XY:
0.0107
AC XY:
794
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.00295
Gnomad4 AMR
AF:
0.00946
Gnomad4 ASJ
AF:
0.000578
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00643
Gnomad4 FIN
AF:
0.0105
Gnomad4 NFE
AF:
0.0191
Gnomad4 OTH
AF:
0.00995
Alfa
AF:
0.0161
Hom.:
22
Bravo
AF:
0.0111
TwinsUK
AF:
0.0132
AC:
49
ALSPAC
AF:
0.0187
AC:
72
ESP6500AA
AF:
0.00190
AC:
7
ESP6500EA
AF:
0.0204
AC:
167
ExAC
?
    Exome Aggregation Consortium database
AF:
0.0111
AC:
1335
Asia WGS
AF:
0.00375
AC:
13
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.45
Cadd
Benign
14
Dann
Benign
0.77
Eigen
Pathogenic
0.81
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.86
D
MutationTaster
Benign
1.0
N;N;N
Vest4
0.015
GERP RS
3.2

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: rs61757718; hg19: chr12-18800961; COSMIC: COSV56814667; API