rs143873873

Positions:

• chr19-18160954-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005027.4(PIK3R2):​c.451C>T​(p.Pro151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,612,186 control chromosomes in the GnomAD database, including 164 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 0.0045 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (144 hom.)
• Consequence: PIK3R2 NM_005027.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024369657).
• BP6: Variant 19-18160954-C-T is Benign according to our data. Variant chr19-18160954-C-T is described in ClinVar as [Benign]. Clinvar id is 235784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R2	NM_005027.4	c.451C>T	p.Pro151Ser	missense_variant	4/16	ENST00000222254.13	NP_005018.2
PIK3R2	NR_073517.2	n.1006C>T		non_coding_transcript_exon_variant	4/16
PIK3R2	NR_162071.1	n.1006C>T		non_coding_transcript_exon_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13	c.451C>T	p.Pro151Ser	missense_variant	4/16	1	NM_005027.4	ENSP00000222254	P1

Frequencies

GnomAD3 genomes AF: 0.00443 AC: 675 AN: 152224 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.0122 AC: 2977 AN: 244948 Hom.: 115 AF XY: 0.00892 AC XY: 1190 AN XY: 133450

Gnomad AFR exome AF: 0.000651

Gnomad AMR exome AF: 0.0797

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0105

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000544

Gnomad OTH exome AF: 0.00838

GnomAD4 exome AF: 0.00266 AC: 3878 AN: 1459844 Hom.: 144 Cov.: 32 AF XY: 0.00221 AC XY: 1606 AN XY: 726142

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.0724

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0119

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00448 AC: 682 AN: 152342 Hom.: 20 Cov.: 32 AF XY: 0.00514 AC XY: 383 AN XY: 74492

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.0393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00675

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.000855 Hom.: 1

Bravo AF: 0.00770

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00924 AC: 1119

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 13, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.66
DEOGEN2	Benign	0.064	T;T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.70	.;T;.
MetaRNN	Benign	0.0024	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.9	N;.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.46	N;.;.
REVEL	Benign	0.13
Sift	Benign	0.74	T;.;.
Sift4G	Benign	0.46	T;T;T
Polyphen		0.0060	B;.;B
Vest4		0.29
MPC		0.29
ClinPred		0.0080	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.20

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

Other links and lift over

dbSNP: rs143873873; hg19: chr19-18271764;