rs143873873

Variant names:

Variant summary

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

The NM_005027.4(PIK3R2):c.451C>T(p.Pro151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,612,186 control chromosomes in the GnomAD database, including 164 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 (★★).

Frequency

Genomes: 𝑓 0.0045 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 144 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.35

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:

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=0.0024369657).

BP6

Variant 19-18160954-C-T is Benign according to our data. Variant chr19-18160954-C-T is described in ClinVar as [Benign]. Clinvar id is 235784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R2	NM_005027.4 link	c.451C>T	p.Pro151Ser	missense_variant	Exon 4 of 16	ENST00000222254.13	NP_005018.2	O00459
PIK3R2	NR_073517.2 link	n.1006C>T		non_coding_transcript_exon_variant	Exon 4 of 16
PIK3R2	NR_162071.1 link	n.1006C>T		non_coding_transcript_exon_variant	Exon 4 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 link	c.451C>T	p.Pro151Ser	missense_variant	Exon 4 of 16	1	NM_005027.4	ENSP00000222254.6		O00459
ENSG00000268173	ENST00000593731.1 link	n.451C>T		non_coding_transcript_exon_variant	Exon 4 of 25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

675

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.0122

AC:

2977

AN:

244948

Hom.:

115

AF XY:

0.00892

AC XY:

1190

AN XY:

133450

show subpopulations

Gnomad AFR exome

AF:

0.000651

Gnomad AMR exome

AF:

0.0797

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.00838

GnomAD4 exome

AF:

0.00266

AC:

3878

AN:

1459844

Hom.:

144

Cov.:

AF XY:

0.00221

AC XY:

1606

AN XY:

726142

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.0724

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0119

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00448

AC:

682

AN:

152342

Hom.:

Cov.:

AF XY:

0.00514

AC XY:

383

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.0393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00675

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000855

Hom.:

Bravo

AF:

0.00770

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00924

AC:

1119

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

- -

Jan 13, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Benign:1

Jan 29, 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

0.14

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.064

T;T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.70

.;T;.

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.9

N;.;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.46

N;.;.

REVEL

Benign

0.13

Sift

Benign

0.74

T;.;.

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0060

B;.;B

Vest4

0.29

MPC

0.29

ClinPred

0.0080

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.20

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