rs1555815294

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★★). Synonymous variant affecting the same amino acid position (i.e. H698H) has been classified as Likely benign.

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, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.29

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P, Genomics England PanelApp
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PIK3R2 links:

ENSG00000268173 (HGNC:):

ENSG00000268173 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein
PIK3R2	NM_005027.4 link	c.2093A>C	p.His698Pro	missense_variant	Exon 16 of 16	ENST00000222254.13	NP_005018.2
PIK3R2	NR_073517.2 link	n.2697A>C		non_coding_transcript_exon_variant	Exon 16 of 16
PIK3R2	NR_162071.1 link	n.2435A>C		non_coding_transcript_exon_variant	Exon 15 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 link	c.2093A>C	p.His698Pro	missense_variant	Exon 16 of 16	1	NM_005027.4	ENSP00000222254.6
ENSG00000268173	ENST00000593731.1 link	n.2093A>C		non_coding_transcript_exon_variant	Exon 16 of 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

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5126

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111082

Other (OTH)

AF:

0.00

AC:

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Mar 15, 2016

Center for Personalized Medicine, Children's Hospital Los Angeles

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 11, 2024

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Reported in a patient with aqueductal stenosis, choreoathetosis, and global developmental delay in published literature; however, no segregation information was provided (PMID: 30755392); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30755392) -

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

(source)

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

PhyloP100

7.3

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

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over