19-18162237-T-C

Position:

chr19-18162237-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005027.4(PIK3R2):c.937T>C(p.Ser313Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,601,454 control chromosomes in the GnomAD database, including 722,944 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 69490 hom., cov: 32)

Exomes 𝑓: 0.95 ( 653454 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.00200

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0996432E-6).

BP6

Variant 19-18162237-T-C is Benign according to our data. Variant chr19-18162237-T-C is described in ClinVar as [Benign]. Clinvar id is 803546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-18162237-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R2	NM_005027.4 link	c.937T>C	p.Ser313Pro	missense_variant	8/16	ENST00000222254.13	NP_005018.2	O00459
PIK3R2	NR_073517.2 link	n.1492T>C		non_coding_transcript_exon_variant	8/16
PIK3R2	NR_162071.1 link	n.1275T>C		non_coding_transcript_exon_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 link	c.937T>C	p.Ser313Pro	missense_variant	8/16	1	NM_005027.4	ENSP00000222254.6		O00459
ENSG00000268173	ENST00000593731.1 link	n.937T>C		non_coding_transcript_exon_variant	8/25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes

AF:

0.955

AC:

145316

AN:

152116

Hom.:

69429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.982

Gnomad AMR

AF:

0.963

Gnomad ASJ

AF:

0.950

Gnomad EAS

AF:

0.965

Gnomad SAS

AF:

0.921

Gnomad FIN

AF:

0.956

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.959

GnomAD3 exomes

AF:

0.952

AC:

234355

AN:

246170

Hom.:

111614

AF XY:

0.949

AC XY:

126784

AN XY:

133580

show subpopulations

Gnomad AFR exome

AF:

0.968

Gnomad AMR exome

AF:

0.973

Gnomad ASJ exome

AF:

0.947

Gnomad EAS exome

AF:

0.967

Gnomad SAS exome

AF:

0.922

Gnomad FIN exome

AF:

0.953

Gnomad NFE exome

AF:

0.949

Gnomad OTH exome

AF:

0.946

GnomAD4 exome

AF:

0.949

AC:

1375848

AN:

1449220

Hom.:

653454

Cov.:

AF XY:

0.948

AC XY:

683561

AN XY:

720998

show subpopulations

Gnomad4 AFR exome

AF:

0.965

Gnomad4 AMR exome

AF:

0.971

Gnomad4 ASJ exome

AF:

0.949

Gnomad4 EAS exome

AF:

0.963

Gnomad4 SAS exome

AF:

0.919

Gnomad4 FIN exome

AF:

0.952

Gnomad4 NFE exome

AF:

0.950

Gnomad4 OTH exome

AF:

0.950

GnomAD4 genome

AF:

0.955

AC:

145437

AN:

152234

Hom.:

69490

Cov.:

AF XY:

0.955

AC XY:

71075

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.967

Gnomad4 AMR

AF:

0.963

Gnomad4 ASJ

AF:

0.950

Gnomad4 EAS

AF:

0.965

Gnomad4 SAS

AF:

0.921

Gnomad4 FIN

AF:

0.956

Gnomad4 NFE

AF:

0.948

Gnomad4 OTH

AF:

0.960

Alfa

AF:

0.950

Hom.:

102168

Bravo

AF:

0.957

TwinsUK

AF:

0.947

AC:

3512

ALSPAC

AF:

0.954

AC:

3677

ESP6500AA

AF:

0.969

AC:

4267

ESP6500EA

AF:

0.948

AC:

8150

ExAC

AF:

0.949

AC:

115094

Asia WGS

AF:

0.943

AC:

3279

AN:

3478

EpiCase

AF:

0.949

EpiControl

AF:

0.946

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.5

DANN

Benign

0.067

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.052

.;T;.

MetaRNN

Benign

0.0000011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

N;.;N

PrimateAI

Benign

0.40

PROVEAN

Benign

1.7

N;.;.

REVEL

Benign

0.024

Sift

Benign

0.72

T;.;.

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.028

MPC

0.35

ClinPred

0.00060

GERP RS

-2.0

Varity_R

0.038

gMVP

0.33

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