dbSNP rs1308748759: PIK3R2:p.Leu12Met (chr19-18155913-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005027.4(PIK3R2):c.34C>A(p.Leu12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. L12V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

1 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: G2P, Labcorp Genetics (formerly Invitae), Illumina, 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24221).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005027.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3R2	NM_005027.4	MANE Select	c.34C>A	p.Leu12Met	missense	Exon 2 of 16	NP_005018.2	O00459
PIK3R2	NR_073517.2		n.589C>A		non_coding_transcript_exon	Exon 2 of 16
PIK3R2	NR_162071.1		n.589C>A		non_coding_transcript_exon	Exon 2 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3R2	ENST00000222254.13	TSL:1 MANE Select	c.34C>A	p.Leu12Met	missense	Exon 2 of 16	ENSP00000222254.6	O00459
ENSG00000268173	ENST00000593731.1	TSL:2	n.34C>A		non_coding_transcript_exon	Exon 2 of 25	ENSP00000471914.1
PIK3R2	ENST00000617130.6	TSL:1	n.34C>A		non_coding_transcript_exon	Exon 2 of 15	ENSP00000477864.2	A0A7I2U3A3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1412626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698462

African (AFR)

AF:

0.00

AC:

AN:

32098

American (AMR)

AF:

0.00

AC:

AN:

38020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25258

East Asian (EAS)

AF:

0.00

AC:

AN:

36802

South Asian (SAS)

AF:

0.00

AC:

AN:

80564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087102

Other (OTH)

AF:

0.00

AC:

AN:

58504

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.096

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.037

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

2.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.67

REVEL

Benign

0.065

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0070

Polyphen

0.76

Vest4

0.35

MutPred

0.32

Gain of disorder (P = 0.0474)

MVP

0.29

MPC

0.63

ClinPred

0.75

GERP RS

0.80

Varity_R

0.26

gMVP

0.38

Mutation Taster

=87/13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over