Menu
GeneBe

rs2230735

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005026.5(PIK3CD):ā€‹c.678A>Gā€‹(p.Thr226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,610,348 control chromosomes in the GnomAD database, including 574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.037 ( 233 hom., cov: 33)
Exomes š‘“: 0.0075 ( 341 hom. )

Consequence

PIK3CD
NM_005026.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.09
Variant links:
Genes affected
PIK3CD (HGNC:8977): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 1-9716517-A-G is Benign according to our data. Variant chr1-9716517-A-G is described in ClinVar as [Benign]. Clinvar id is 474033.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-5.09 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIK3CDNM_005026.5 linkuse as main transcriptc.678A>G p.Thr226= synonymous_variant 6/24 ENST00000377346.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIK3CDENST00000377346.9 linkuse as main transcriptc.678A>G p.Thr226= synonymous_variant 6/241 NM_005026.5 P3O00329-1

Frequencies

GnomAD3 genomes
AF:
0.0366
AC:
5577
AN:
152170
Hom.:
230
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0197
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.0429
Gnomad SAS
AF:
0.00517
Gnomad FIN
AF:
0.0412
Gnomad MID
AF:
0.0411
Gnomad NFE
AF:
0.00207
Gnomad OTH
AF:
0.0296
GnomAD3 exomes
AF:
0.0182
AC:
4479
AN:
246058
Hom.:
121
AF XY:
0.0151
AC XY:
2020
AN XY:
134148
show subpopulations
Gnomad AFR exome
AF:
0.111
Gnomad AMR exome
AF:
0.0200
Gnomad ASJ exome
AF:
0.000302
Gnomad EAS exome
AF:
0.0419
Gnomad SAS exome
AF:
0.00497
Gnomad FIN exome
AF:
0.0381
Gnomad NFE exome
AF:
0.00234
Gnomad OTH exome
AF:
0.0140
GnomAD4 exome
AF:
0.00753
AC:
10982
AN:
1458060
Hom.:
341
Cov.:
33
AF XY:
0.00710
AC XY:
5148
AN XY:
725350
show subpopulations
Gnomad4 AFR exome
AF:
0.113
Gnomad4 AMR exome
AF:
0.0198
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.0513
Gnomad4 SAS exome
AF:
0.00453
Gnomad4 FIN exome
AF:
0.0373
Gnomad4 NFE exome
AF:
0.000979
Gnomad4 OTH exome
AF:
0.0128
GnomAD4 genome
AF:
0.0367
AC:
5596
AN:
152288
Hom.:
233
Cov.:
33
AF XY:
0.0381
AC XY:
2835
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.106
Gnomad4 AMR
AF:
0.0196
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.0430
Gnomad4 SAS
AF:
0.00518
Gnomad4 FIN
AF:
0.0412
Gnomad4 NFE
AF:
0.00207
Gnomad4 OTH
AF:
0.0298
Alfa
AF:
0.0166
Hom.:
51
Bravo
AF:
0.0400
Asia WGS
AF:
0.0290
AC:
99
AN:
3478
EpiCase
AF:
0.00185
EpiControl
AF:
0.00237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Immunodeficiency 14 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.11
DANN
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2230735; hg19: chr1-9776575; COSMIC: COSV100739991; COSMIC: COSV100739991; API