Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_005026.5(PIK3CD):c.1246T>C(p.Cys416Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

PIK3CD
NM_005026.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.06

Publications

31 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-9719924-T-C is Pathogenic according to our data. Variant chr1-9719924-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 132808.Status of the report is no_assertion_criteria_provided, 0 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.1246T>C	p.Cys416Arg	missense	Exon 10 of 24	NP_005017.3
PIK3CD	NM_001437546.1		c.1246T>C	p.Cys416Arg	missense	Exon 9 of 23	NP_001424475.1
PIK3CD	NM_001350234.2		c.1246T>C	p.Cys416Arg	missense	Exon 10 of 24	NP_001337163.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIK3CD	ENST00000377346.9	TSL:1 MANE Select	c.1246T>C	p.Cys416Arg	missense	Exon 10 of 24	ENSP00000366563.4
PIK3CD	ENST00000361110.6	TSL:1	c.1141T>C	p.Cys381Arg	missense	Exon 9 of 23	ENSP00000354410.2
PIK3CD	ENST00000698712.1		c.1246T>C	p.Cys416Arg	missense	Exon 9 of 23	ENSP00000513889.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.000131

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.60

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.9

PhyloP100

5.1

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.4

REVEL

Pathogenic

0.82

Sift

Benign

0.30

Sift4G

Benign

0.28

Polyphen

1.0

Vest4

0.54

MutPred

0.63

Gain of MoRF binding (P = 0.0066)

MVP

0.69

MPC

2.7

ClinPred

0.98

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.94

Mutation Taster

=4/96

disease causing (ClinVar)

(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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rs587777390

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over