rs142285826

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_005026.5(PIK3CD):c.436T>A(p.Phe146Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000925 in 1,582,446 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

PIK3CD
NM_005026.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.77

Publications

2 publications found

Variant links:

COSMIC-nc: COSV100740203

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]

PIK3CD Gene-Disease associations (from GenCC):

immunodeficiency 14
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
immunodeficiency 14b, autosomal recessive
Inheritance: AR, Unknown Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
activated PI3K-delta syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PIK3CD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010897398).

BP6

Variant 1-9715914-T-A is Benign according to our data. Variant chr1-9715914-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005026.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIK3CD	NM_005026.5	MANE Select	c.436T>A	p.Phe146Ile	missense	Exon 5 of 24	NP_005017.3
PIK3CD	NM_001437546.1		c.436T>A	p.Phe146Ile	missense	Exon 4 of 23	NP_001424475.1
PIK3CD	NM_001350234.2		c.436T>A	p.Phe146Ile	missense	Exon 5 of 24	NP_001337163.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIK3CD	ENST00000377346.9	TSL:1 MANE Select	c.436T>A	p.Phe146Ile	missense	Exon 5 of 24	ENSP00000366563.4
PIK3CD	ENST00000361110.6	TSL:1	c.436T>A	p.Phe146Ile	missense	Exon 4 of 23	ENSP00000354410.2
PIK3CD	ENST00000698712.1		c.436T>A	p.Phe146Ile	missense	Exon 4 of 23	ENSP00000513889.1

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

169

AN:

149560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000200

Gnomad ASJ

AF:

0.00290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00511

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.000483

GnomAD2 exomes

AF:

0.00118

AC:

287

AN:

243346

AF XY:

0.00104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.00122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.000838

GnomAD4 exome

AF:

0.000903

AC:

1294

AN:

1432748

Hom.:

Cov.:

AF XY:

0.000894

AC XY:

637

AN XY:

712542

show subpopulations

African (AFR)

AF:

0.0000615

AC:

AN:

32510

American (AMR)

AF:

0.0000687

AC:

AN:

43692

Ashkenazi Jewish (ASJ)

AF:

0.00140

AC:

AN:

25078

East Asian (EAS)

AF:

0.00

AC:

AN:

37926

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86016

European-Finnish (FIN)

AF:

0.00612

AC:

301

AN:

49222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.000823

AC:

901

AN:

1094308

Other (OTH)

AF:

0.000874

AC:

AN:

58382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

184

276

368

460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00113

AC:

169

AN:

149698

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

73134

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41114

American (AMR)

AF:

0.000199

AC:

AN:

15042

Ashkenazi Jewish (ASJ)

AF:

0.00290

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4800

South Asian (SAS)

AF:

0.00

AC:

AN:

4498

European-Finnish (FIN)

AF:

0.00511

AC:

AN:

10180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00151

AC:

102

AN:

67332

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00138

AC:

167

EpiCase

AF:

0.00109

EpiControl

AF:

0.000534

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 14 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

M_CAP

Benign

0.016

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

5.8

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.010

REVEL

Benign

0.17

Sift

Benign

0.28

Sift4G

Benign

0.67

Polyphen

0.33

Vest4

0.67

MVP

0.75

MPC

1.5

ClinPred

0.027

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.80

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over