19-18169286-G-C

Position:

• chr19-18169286-G-C

Variant summary

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

The ENST00000222254.13(PIK3R2):​c.2179G>C​(p.Ala727Pro) 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. 12/21 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. A727T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIK3R2 ENST00000222254.13 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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=0.09362489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R2	NM_005027.4	c.2179G>C	p.Ala727Pro	missense_variant	16/16	ENST00000222254.13	NP_005018.2
PIK3R2	NR_073517.2	n.2783G>C		non_coding_transcript_exon_variant	16/16
PIK3R2	NR_162071.1	n.2521G>C		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13	c.2179G>C	p.Ala727Pro	missense_variant	16/16	1	NM_005027.4	ENSP00000222254	P1
PIK3R2	ENST00000617130.5	c.*1207G>C		3_prime_UTR_variant, NMD_transcript_variant	15/15	1		ENSP00000477864
PIK3R2	ENST00000426902.5	c.*782G>C		3_prime_UTR_variant, NMD_transcript_variant	15/15	2		ENSP00000395636
PIK3R2	ENST00000617642.2	c.*1207G>C		3_prime_UTR_variant, NMD_transcript_variant	14/14	5		ENSP00000484714

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.088	N
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.16	N;.
REVEL	Benign	0.053
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.14	T;T
Polyphen		0.11	B;B
Vest4		0.22
MutPred		0.20		Gain of glycosylation at A727 (P = 0.0063);Gain of glycosylation at A727 (P = 0.0063);
MVP		0.25
MPC		1.1
ClinPred		0.19	T
GERP RS		-2.8
Varity_R		0.20
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-18280096;