rs149081991

Positions:

Variant summary

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

The NM_005027.4(PIK3R2):c.2179G>A(p.Ala727Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 1,495,138 control chromosomes in the GnomAD database, including 1,847 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 0.038 ( 151 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1696 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0820

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:

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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=0.0014354289).

BP6

Variant 19-18169286-G-A is Benign according to our data. Variant chr19-18169286-G-A is described in ClinVar as [Benign]. Clinvar id is 468323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-18169286-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIK3R2	NM_005027.4 linkuse as main transcript	c.2179G>A	p.Ala727Thr	missense_variant	16/16	ENST00000222254.13
PIK3R2	NR_073517.2 linkuse as main transcript	n.2783G>A		non_coding_transcript_exon_variant	16/16
PIK3R2	NR_162071.1 linkuse as main transcript	n.2521G>A		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIK3R2	ENST00000222254.13 linkuse as main transcript	c.2179G>A	p.Ala727Thr	missense_variant	16/16	1	NM_005027.4	P1
PIK3R2	ENST00000617130.5 linkuse as main transcript	c.*1207G>A		3_prime_UTR_variant, NMD_transcript_variant	15/15	1
PIK3R2	ENST00000426902.5 linkuse as main transcript	c.*782G>A		3_prime_UTR_variant, NMD_transcript_variant	15/15	2
PIK3R2	ENST00000617642.2 linkuse as main transcript	c.*1207G>A		3_prime_UTR_variant, NMD_transcript_variant	14/14	5

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5819

AN:

151832

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00918

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.0828

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0855

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0502

Gnomad OTH

AF:

0.0422

GnomAD3 exomes

AF:

0.0420

AC:

4305

AN:

102418

Hom.:

150

AF XY:

0.0411

AC XY:

2330

AN XY:

56684

show subpopulations

Gnomad AFR exome

AF:

0.00954

Gnomad AMR exome

AF:

0.0355

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.000344

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.0779

Gnomad NFE exome

AF:

0.0573

Gnomad OTH exome

AF:

0.0508

GnomAD4 exome

AF:

0.0451

AC:

60598

AN:

1343198

Hom.:

1696

Cov.:

AF XY:

0.0446

AC XY:

29493

AN XY:

661842

show subpopulations

Gnomad4 AFR exome

AF:

0.00765

Gnomad4 AMR exome

AF:

0.0348

Gnomad4 ASJ exome

AF:

0.0936

Gnomad4 EAS exome

AF:

0.000118

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.0714

Gnomad4 NFE exome

AF:

0.0481

Gnomad4 OTH exome

AF:

0.0468

GnomAD4 genome

AF:

0.0383

AC:

5818

AN:

151940

Hom.:

151

Cov.:

AF XY:

0.0400

AC XY:

2974

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00915

Gnomad4 AMR

AF:

0.0436

Gnomad4 ASJ

AF:

0.0828

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.0855

Gnomad4 NFE

AF:

0.0502

Gnomad4 OTH

AF:

0.0418

Alfa

AF:

0.0473

Hom.:

Bravo

AF:

0.0341

TwinsUK

AF:

0.0434

AC:

161

ALSPAC

AF:

0.0467

AC:

180

ESP6500AA

AF:

0.0110

AC:

ESP6500EA

AF:

0.0472

AC:

210

ExAC

AF:

0.0282

AC:

1734

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.029

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.71

N;.

REVEL

Benign

0.042

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.21

T;T

Polyphen

0.0

B;B

Vest4

0.050

MPC

0.80

ClinPred

0.021

GERP RS

-2.8

Varity_R

0.16

gMVP

0.12

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