rs28730848

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 Benign. Variant got -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 id is 468326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-18162203-G-A is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.0430

AC:

10290

AN:

239038

Hom.:

288

AF XY:

0.0460

AC XY:

5970

AN XY:

129674

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 SAS exome

AF:

0.0659

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

Gnomad4 AFR exome

AF:

0.00818

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.0487

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.0682

Gnomad4 FIN exome

AF:

0.0393

Gnomad4 NFE exome

AF:

0.0549

Gnomad4 OTH exome

AF:

0.0472

GnomAD4 genome

AF:

0.0377

AC:

5745

AN:

152246

Hom.:

155

Cov.:

AF XY:

0.0369

AC XY:

2744

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00934

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0579

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0667

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.0572

Gnomad4 OTH

AF:

0.0366

Alfa

AF:

0.0486

Hom.:

291

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.4

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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