rs28730848

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005027.4(PIK3R2):c.903G>A(p.Ala301Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,547,836 control chromosomes in the GnomAD database, including 2,181 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A301A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.038 ( 155 hom., cov: 33)

Exomes 𝑓: 0.051 ( 2026 hom. )

Consequence

PIK3R2
NM_005027.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001386

Clinical Significance

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

Conservation

PhyloP100: -2.40

Publications

8 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-18162203-G-A is Benign according to our data. Variant chr19-18162203-G-A is described in ClinVar as Benign. ClinVar VariationId is 468326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R2	NM_005027.4 link	c.903G>A	p.Ala301Ala	splice_region_variant, synonymous_variant	Exon 8 of 16	ENST00000222254.13	NP_005018.2	O00459
PIK3R2	NR_073517.2 link	n.1458G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 8 of 16
PIK3R2	NR_162071.1 link	n.1241G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 7 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 link	c.903G>A	p.Ala301Ala	splice_region_variant, synonymous_variant	Exon 8 of 16	1	NM_005027.4	ENSP00000222254.6		O00459
ENSG00000268173	ENST00000593731.1 link	n.903G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 8 of 25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes

AF:

0.0378

AC:

5746

AN:

152128

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00937

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0663

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0572

Gnomad OTH

AF:

0.0369

GnomAD2 exomes

AF:

0.0430

AC:

10290

AN:

239038

AF XY:

0.0460

show subpopulations

Gnomad AFR exome

AF:

0.00778

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0489

Gnomad EAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.0385

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0465

GnomAD4 exome

AF:

0.0509

AC:

71041

AN:

1395590

Hom.:

2026

Cov.:

AF XY:

0.0521

AC XY:

36264

AN XY:

695802

show subpopulations

African (AFR)

AF:

0.00818

AC:

265

AN:

32408

American (AMR)

AF:

0.0191

AC:

838

AN:

43912

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

1221

AN:

25080

East Asian (EAS)

AF:

0.000178

AC:

AN:

39332

South Asian (SAS)

AF:

0.0682

AC:

5740

AN:

84222

European-Finnish (FIN)

AF:

0.0393

AC:

2074

AN:

52724

Middle Eastern (MID)

AF:

0.0561

AC:

310

AN:

5522

European-Non Finnish (NFE)

AF:

0.0549

AC:

57848

AN:

1054412

Other (OTH)

AF:

0.0472

AC:

2738

AN:

57978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3130

6259

9389

12518

15648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2056

4112

6168

8224

10280

<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

AF:

0.0377

AC:

5745

AN:

152246

Hom.:

155

Cov.:

AF XY:

0.0369

AC XY:

2744

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00934

AC:

388

AN:

41552

American (AMR)

AF:

0.0226

AC:

345

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.0667

AC:

322

AN:

4824

European-Finnish (FIN)

AF:

0.0395

AC:

419

AN:

10614

Middle Eastern (MID)

AF:

0.0890

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0572

AC:

3890

AN:

68006

Other (OTH)

AF:

0.0366

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

278

556

835

1113

1391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0478

Hom.:

460

Bravo

AF:

0.0344

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Aug 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.4

(source)

DANN

Benign

0.70

PhyloP100

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=83/17

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0060

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over