chr19-18161401-C-T

Position:

• chr19-18161401-C-T

Variant summary

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

The NM_005027.4(PIK3R2):​c.721C>T​(p.Pro241Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000935 in 1,070,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: PIK3R2 NM_005027.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983

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]

ENSG00000268173 (HGNC:):

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=0.09442276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R2	NM_005027.4	c.721C>T	p.Pro241Ser	missense_variant	6/16	ENST00000222254.13	NP_005018.2
PIK3R2	NR_073517.2	n.1276C>T		non_coding_transcript_exon_variant	6/16
PIK3R2	NR_162071.1	n.1153+216C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13	c.721C>T	p.Pro241Ser	missense_variant	6/16	1	NM_005027.4	ENSP00000222254.6
ENSG00000268173	ENST00000593731.1	n.721C>T		non_coding_transcript_exon_variant	6/25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.35e-7 AC: 1 AN: 1070008 Hom.: 0 Cov.: 33 AF XY: 0.00000196 AC XY: 1 AN XY: 509280

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000109

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.059	T;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.63	.;T;.
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.28	N;.;.
REVEL	Benign	0.039
Sift	Benign	0.17	T;.;.
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.015
MutPred		0.52		Gain of MoRF binding (P = 0.0311);Gain of MoRF binding (P = 0.0311);Gain of MoRF binding (P = 0.0311);
MVP		0.082
MPC		0.29
ClinPred		0.13	T
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1168878327; hg19: chr19-18272211;