Genetic Variant PIK3R2:p.Ser234Cys (chr19-18161380-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005027.4(PIK3R2):c.700A>T(p.Ser234Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,091,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S234R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10293162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R2	NM_005027.4 link	c.700A>T	p.Ser234Cys	missense_variant	Exon 6 of 16	ENST00000222254.13	NP_005018.2	O00459
PIK3R2	NR_073517.2 link	n.1255A>T		non_coding_transcript_exon_variant	Exon 6 of 16
PIK3R2	NR_162071.1 link	n.1153+195A>T		intron_variant	Intron 5 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 link	c.700A>T	p.Ser234Cys	missense_variant	Exon 6 of 16	1	NM_005027.4	ENSP00000222254.6		O00459
ENSG00000268173	ENST00000593731.1 link	n.700A>T		non_coding_transcript_exon_variant	Exon 6 of 25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1091682

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

520454

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:

0.00000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.18

.;T;.

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;L

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.84

N;.;.

REVEL

Benign

0.030

Sift

Uncertain

0.0030

D;.;.

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

0.0

B;.;B

Vest4

0.057

MutPred

0.43

Loss of phosphorylation at S234 (P = 0.0344);Loss of phosphorylation at S234 (P = 0.0344);Loss of phosphorylation at S234 (P = 0.0344);

MVP

0.10

MPC

0.66

ClinPred

0.51

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over