19-18156039-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005027.4(PIK3R2):c.160G>C(p.Val54Leu) 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. 14/21 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. V54M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3R2 NM_005027.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

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 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=0.1414586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R2	NM_005027.4	c.160G>C	p.Val54Leu	missense_variant	2/16	ENST00000222254.13
PIK3R2	NR_073517.2	n.715G>C		non_coding_transcript_exon_variant	2/16
PIK3R2	NR_162071.1	n.715G>C		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R2	ENST00000222254.13	c.160G>C	p.Val54Leu	missense_variant	2/16	1	NM_005027.4	P1
PIK3R2	ENST00000617130.5	c.160G>C	p.Val54Leu	missense_variant, NMD_transcript_variant	2/15	1
PIK3R2	ENST00000426902.5	c.160G>C	p.Val54Leu	missense_variant, NMD_transcript_variant	1/15	2
PIK3R2	ENST00000617642.2	c.160G>C	p.Val54Leu	missense_variant, NMD_transcript_variant	2/14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	21
Dann	Benign	0.97
DEOGEN2	Benign	0.15	T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.90	N;.;N
MutationTaster	Benign	0.90	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.35	N;.;.
REVEL	Benign	0.073
Sift	Benign	0.17	T;.;.
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0020	B;.;B
Vest4		0.098
MutPred		0.35		Gain of catalytic residue at V54 (P = 0.05);Gain of catalytic residue at V54 (P = 0.05);Gain of catalytic residue at V54 (P = 0.05);
MVP		0.17
MPC		0.27
ClinPred		0.47	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.12

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.

Other links and lift over

hg19: chr19-18266849;