Variant rs765672206 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_005027.4(PIK3R2):c.1543G>A(p.Glu515Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.52

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIK3R2	NM_005027.4 linkuse as main transcript	c.1543G>A	p.Glu515Lys	missense_variant	12/16	ENST00000222254.13
PIK3R2	NR_073517.2 linkuse as main transcript	n.2147G>A		non_coding_transcript_exon_variant	12/16
PIK3R2	NR_162071.1 linkuse as main transcript	n.1881G>A		non_coding_transcript_exon_variant	11/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R2	ENST00000222254.13 linkuse as main transcript	c.1543G>A	p.Glu515Lys	missense_variant	12/16	1	NM_005027.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250502

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Feb 04, 2017

In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs765672206, ExAC 0.006%) but has not been reported in the literature in individuals with a PIK3R2-related disease. This sequence change replaces glutamic acid with lysine at codon 515 of the PIK3R2 protein (p.Glu515Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.25

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.10

Sift

Benign

0.058

T;.

Sift4G

Benign

0.20

T;T

Polyphen

0.99

D;D

Vest4

0.59

MutPred

0.21

Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);

MVP

0.48

MPC

1.1

ClinPred

0.79

GERP RS

4.4

Varity_R

0.30

gMVP

0.25

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