Variant rs139848768 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005026.5(PIK3CD):c.2319C>T(p.Ser773=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,612,866 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 12 hom., cov: 32)

Exomes 𝑓: 0.016 ( 251 hom. )

Consequence

PIK3CD
NM_005026.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.369

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-9722328-C-T is Benign according to our data. Variant chr1-9722328-C-T is described in ClinVar as [Benign]. Clinvar id is 474026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.369 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1783/152066) while in subpopulation NFE AF= 0.019 (1293/67948). AF 95% confidence interval is 0.0182. There are 12 homozygotes in gnomad4. There are 830 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CD	NM_005026.5 linkuse as main transcript	c.2319C>T	p.Ser773=	synonymous_variant	18/24	ENST00000377346.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CD	ENST00000377346.9 linkuse as main transcript	c.2319C>T	p.Ser773=	synonymous_variant	18/24	1	NM_005026.5	P3	O00329-1

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1783

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.00959

GnomAD3 exomes

AF:

0.0105

AC:

2583

AN:

247022

Hom.:

AF XY:

0.0105

AC XY:

1413

AN XY:

134300

show subpopulations

Gnomad AFR exome

AF:

0.00279

Gnomad AMR exome

AF:

0.00757

Gnomad ASJ exome

AF:

0.0161

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00269

Gnomad FIN exome

AF:

0.00328

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

AF:

0.0163

AC:

23838

AN:

1460800

Hom.:

251

Cov.:

AF XY:

0.0161

AC XY:

11666

AN XY:

726690

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.00768

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00349

Gnomad4 FIN exome

AF:

0.00411

Gnomad4 NFE exome

AF:

0.0195

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.0117

AC:

1783

AN:

152066

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

830

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00376

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00415

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.00949

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0164

EpiControl

AF:

0.0168

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 26, 2023

- -

PIK3CD-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Immunodeficiency 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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