rs61755420

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005026.5(PIK3CD):c.935C>G(p.Ser312Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,613,884 control chromosomes in the GnomAD database, including 660 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S312S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.019 ( 45 hom., cov: 32)

Exomes 𝑓: 0.027 ( 615 hom. )

Consequence

PIK3CD
NM_005026.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.09

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]

PIK3CD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024999976).

BP6

Variant 1-9717541-C-G is Benign according to our data. Variant chr1-9717541-C-G is described in ClinVar as [Benign]. Clinvar id is 440066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0187 (2851/152378) while in subpopulation NFE AF= 0.027 (1834/68042). AF 95% confidence interval is 0.0259. There are 45 homozygotes in gnomad4. There are 1338 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CD	NM_005026.5 link	c.935C>G	p.Ser312Cys	missense_variant	Exon 8 of 24	ENST00000377346.9	NP_005017.3	O00329-1A0A2K8FKV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9 link	c.935C>G	p.Ser312Cys	missense_variant	Exon 8 of 24	1	NM_005026.5	ENSP00000366563.4		O00329-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2853

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00509

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0496

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0202

AC:

5055

AN:

250332

Hom.:

AF XY:

0.0203

AC XY:

2748

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.00364

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0476

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.0263

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0270

AC:

39495

AN:

1461506

Hom.:

615

Cov.:

AF XY:

0.0262

AC XY:

19068

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.00391

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0467

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00270

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.0307

Gnomad4 OTH exome

AF:

0.0271

GnomAD4 genome

AF:

0.0187

AC:

2851

AN:

152378

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1338

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00507

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.0496

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0238

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0196

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0309

AC:

119

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.0299

AC:

257

ExAC

AF:

0.0207

AC:

2509

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0295

EpiControl

AF:

0.0313

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PIK3CD: BP4, BS1, BS2 -

Immunodeficiency 14

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.055

.;T;D;.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.33

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.054

.;T;T;T;.

MetaRNN

Benign

0.0025

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;.;L;.;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.6

D;.;N;.;D

REVEL

Benign

0.12

Sift

Benign

0.042

D;.;D;.;D

Sift4G

Uncertain

0.029

D;D;D;D;D

Polyphen

0.0

B;.;P;B;.

Vest4

0.12

MPC

1.6

ClinPred

0.023

GERP RS

3.6

Varity_R

0.21

gMVP

0.55

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over