rs2241088

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005027.4(PIK3R2):c.700A>C(p.Ser234Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 1,241,468 control chromosomes in the GnomAD database, including 536,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65204 hom., cov: 32)

Exomes 𝑓: 0.93 ( 470908 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

PIK3R2 (HGNC:8980): (phosphoinositide-3-kinase regulatory subunit 2) Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that phosphorylates phosphatidylinositol and similar compounds, creating second messengers important in growth signaling pathways. PI3K functions as a heterodimer of a regulatory and a catalytic subunit. The protein encoded by this gene is a regulatory component of PI3K. Three transcript variants, one protein coding and the other two non-protein coding, have been found for this gene. [provided by RefSeq, Apr 2019]

PIK3R2 links:

ENSG00000268173 (HGNC:):

ENSG00000268173 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7992236E-7).

BP6

Variant 19-18161380-A-C is Benign according to our data. Variant chr19-18161380-A-C is described in ClinVar as [Benign]. Clinvar id is 497079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-18161380-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R2	NM_005027.4 link	c.700A>C	p.Ser234Arg	missense_variant	Exon 6 of 16	ENST00000222254.13	NP_005018.2	O00459
PIK3R2	NR_073517.2 link	n.1255A>C		non_coding_transcript_exon_variant	Exon 6 of 16
PIK3R2	NR_162071.1 link	n.1153+195A>C		intron_variant	Intron 5 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 link	c.700A>C	p.Ser234Arg	missense_variant	Exon 6 of 16	1	NM_005027.4	ENSP00000222254.6		O00459
ENSG00000268173	ENST00000593731.1 link	n.700A>C		non_coding_transcript_exon_variant	Exon 6 of 25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes

AF:

0.932

AC:

139727

AN:

149952

Hom.:

65157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.982

Gnomad AMR

AF:

0.892

Gnomad ASJ

AF:

0.931

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.877

Gnomad FIN

AF:

0.875

Gnomad MID

AF:

0.939

Gnomad NFE

AF:

0.930

Gnomad OTH

AF:

0.938

GnomAD3 exomes

AF:

0.885

AC:

8559

AN:

9668

Hom.:

3833

AF XY:

0.885

AC XY:

5548

AN XY:

6266

show subpopulations

Gnomad AFR exome

AF:

0.968

Gnomad AMR exome

AF:

0.873

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.833

Gnomad SAS exome

AF:

0.853

Gnomad FIN exome

AF:

0.855

Gnomad NFE exome

AF:

0.915

Gnomad OTH exome

AF:

0.902

GnomAD4 exome

AF:

0.929

AC:

1013468

AN:

1091408

Hom.:

470908

Cov.:

AF XY:

0.928

AC XY:

482883

AN XY:

520302

show subpopulations

Gnomad4 AFR exome

AF:

0.971

Gnomad4 AMR exome

AF:

0.887

Gnomad4 ASJ exome

AF:

0.924

Gnomad4 EAS exome

AF:

0.928

Gnomad4 SAS exome

AF:

0.867

Gnomad4 FIN exome

AF:

0.884

Gnomad4 NFE exome

AF:

0.931

Gnomad4 OTH exome

AF:

0.927

GnomAD4 genome

AF:

0.932

AC:

139827

AN:

150060

Hom.:

65204

Cov.:

AF XY:

0.926

AC XY:

67862

AN XY:

73274

show subpopulations

Gnomad4 AFR

AF:

0.971

Gnomad4 AMR

AF:

0.892

Gnomad4 ASJ

AF:

0.931

Gnomad4 EAS

AF:

0.910

Gnomad4 SAS

AF:

0.878

Gnomad4 FIN

AF:

0.875

Gnomad4 NFE

AF:

0.930

Gnomad4 OTH

AF:

0.936

Alfa

AF:

0.935

Hom.:

8248

Bravo

AF:

0.937

TwinsUK

AF:

0.940

AC:

3484

ALSPAC

AF:

0.943

AC:

3635

ExAC

AF:

0.826

AC:

6407

Asia WGS

AF:

0.886

AC:

2787

AN:

3146

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 23, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.068

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.066

.;T;.

MetaRNN

Benign

5.8e-7

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

N;.;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.82

N;.;.

REVEL

Benign

0.0090

Sift

Benign

0.32

T;.;.

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.028

MutPred

0.32

Gain of MoRF binding (P = 0.0219);Gain of MoRF binding (P = 0.0219);Gain of MoRF binding (P = 0.0219);

MPC

0.31

ClinPred

0.0014

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.29

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

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