rs28730668

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005026.5(PIK3CD):c.886G>A(p.Val296Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,613,934 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 176 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 155 hom. )

Consequence

PIK3CD
NM_005026.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.851

Publications

9 publications found

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]

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018967688).

BP6

Variant 1-9717064-G-A is Benign according to our data. Variant chr1-9717064-G-A is described in ClinVar as Benign. ClinVar VariationId is 474036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

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.886G>A	p.Val296Ile	missense	Exon 7 of 24	NP_005017.3
PIK3CD	NM_001437546.1		c.886G>A	p.Val296Ile	missense	Exon 6 of 23	NP_001424475.1
PIK3CD	NM_001350234.2		c.886G>A	p.Val296Ile	missense	Exon 7 of 24	NP_001337163.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIK3CD	ENST00000377346.9	TSL:1 MANE Select	c.886G>A	p.Val296Ile	missense	Exon 7 of 24	ENSP00000366563.4
PIK3CD	ENST00000361110.6	TSL:1	c.781G>A	p.Val261Ile	missense splice_region	Exon 6 of 23	ENSP00000354410.2
PIK3CD	ENST00000698712.1		c.886G>A	p.Val296Ile	missense	Exon 6 of 23	ENSP00000513889.1

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4138

AN:

152176

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.00740

AC:

1859

AN:

251366

AF XY:

0.00563

show subpopulations

Gnomad AFR exome

AF:

0.0937

Gnomad AMR exome

AF:

0.00584

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00310

AC:

4536

AN:

1461640

Hom.:

155

Cov.:

AF XY:

0.00284

AC XY:

2067

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.0958

AC:

3207

AN:

33478

American (AMR)

AF:

0.00628

AC:

281

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00524

AC:

137

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000255

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53186

Middle Eastern (MID)

AF:

0.00832

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000390

AC:

434

AN:

1112002

Other (OTH)

AF:

0.00672

AC:

406

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

268

536

805

1073

1341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.0272

AC:

4143

AN:

152294

Hom.:

176

Cov.:

AF XY:

0.0267

AC XY:

1988

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0927

AC:

3851

AN:

41542

American (AMR)

AF:

0.0125

AC:

192

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68024

Other (OTH)

AF:

0.0175

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

198

396

595

793

991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0127

Hom.:

119

Bravo

AF:

0.0311

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0881

AC:

388

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00857

AC:

1040

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Immunodeficiency 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.24

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

0.85

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.40

REVEL

Benign

0.023

Sift

Benign

0.44

Sift4G

Benign

0.81

Polyphen

0.057

Vest4

0.092

MVP

0.40

MPC

0.76

ClinPred

0.0030

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.25

Mutation Taster

=82/18

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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