Variant rs1555815294 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005027.4(PIK3R2):c.2093A>C(p.His698Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R2	NM_005027.4 linkuse as main transcript	c.2093A>C	p.His698Pro	missense_variant	16/16	ENST00000222254.13	NP_005018.2	O00459
PIK3R2	NR_073517.2 linkuse as main transcript	n.2697A>C		non_coding_transcript_exon_variant	16/16
PIK3R2	NR_162071.1 linkuse as main transcript	n.2435A>C		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 linkuse as main transcript	c.2093A>C	p.His698Pro	missense_variant	16/16	1	NM_005027.4	ENSP00000222254.6		O00459
ENSG00000268173	ENST00000593731.1 linkuse as main transcript	n.2093A>C		non_coding_transcript_exon_variant	16/25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454656

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Choreoathetosis;C0266476:Aqueductal stenosis;C0557874:Global developmental delay

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Personalized Medicine, Children's Hospital Los Angeles

Mar 15, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.77

D;D

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.063

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.7

D;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.015

D;.

Sift4G

Uncertain

0.028

D;D

Polyphen

1.0

D;D

Vest4

0.65

MutPred

0.43

Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);

MVP

0.54

MPC

2.0

ClinPred

0.99

GERP RS

3.0

Varity_R

0.88

gMVP

0.74

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