19-18155934-C-T

Position:

chr19-18155934-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_005027.4(PIK3R2):c.55C>T(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,569,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PIK3R2
NM_005027.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.57

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1584509).

BP6

Variant 19-18155934-C-T is Benign according to our data. Variant chr19-18155934-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2038641.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000233 (33/1417048) while in subpopulation MID AF= 0.00035 (2/5712). AF 95% confidence interval is 0.0000615. There are 0 homozygotes in gnomad4_exome. There are 21 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIK3R2	NM_005027.4 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant	2/16	ENST00000222254.13
PIK3R2	NR_073517.2 linkuse as main transcript	n.610C>T		non_coding_transcript_exon_variant	2/16
PIK3R2	NR_162071.1 linkuse as main transcript	n.610C>T		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIK3R2	ENST00000222254.13 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant	2/16	1	NM_005027.4	P1
PIK3R2	ENST00000617130.5 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant, NMD_transcript_variant	2/15	1
PIK3R2	ENST00000426902.5 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant, NMD_transcript_variant	1/15	2
PIK3R2	ENST00000617642.2 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant, NMD_transcript_variant	2/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000231

AC:

AN:

173468

Hom.:

AF XY:

0.0000212

AC XY:

AN XY:

94446

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000411

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000430

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1417048

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

701132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.0000220

Gnomad4 OTH exome

AF:

0.0000341

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000174

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.043

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

L;.;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

N;.;.

REVEL

Benign

0.12

Sift

Benign

0.075

T;.;.

Sift4G

Uncertain

0.050

T;D;T

Polyphen

1.0

D;.;D

Vest4

0.27

MutPred

0.38

Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);

MVP

0.34

MPC

0.31

ClinPred

0.70

GERP RS

3.3

Varity_R

0.59

gMVP

0.55

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