19-18169200-A-T

Position:

• chr19-18169200-A-T

Variant summary

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

The NM_005027.4(PIK3R2):​c.2093A>T​(p.His698Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. H698P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIK3R2 NM_005027.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R2	NM_005027.4	c.2093A>T	p.His698Leu	missense_variant	16/16	ENST00000222254.13
PIK3R2	NR_073517.2	n.2697A>T		non_coding_transcript_exon_variant	16/16
PIK3R2	NR_162071.1	n.2435A>T		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R2	ENST00000222254.13	c.2093A>T	p.His698Leu	missense_variant	16/16	1	NM_005027.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.76	D;D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Benign	0.28
Sift	Benign	0.12	T;.
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.46		Loss of disorder (P = 0.1284);Loss of disorder (P = 0.1284);
MVP		0.54
MPC		1.1
ClinPred		0.97	D
GERP RS		3.0
Varity_R		0.48
gMVP		0.42

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: chr19-18280010;