chr19-18167956-C-G

Position:

• chr19-18167956-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005027.4(PIK3R2):​c.1737-519C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,040 control chromosomes in the GnomAD database, including 21,538 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21538 hom., cov: 32)
• Consequence: PIK3R2 NM_005027.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R2	NM_005027.4	c.1737-519C>G		intron_variant		ENST00000222254.13	NP_005018.2
PIK3R2	NR_073517.2	n.2341-519C>G		intron_variant, non_coding_transcript_variant
PIK3R2	NR_162071.1	n.2075-519C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13	c.1737-519C>G		intron_variant		1	NM_005027.4	ENSP00000222254	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80393 AN: 151920 Hom.: 21526 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.496

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.529 AC: 80456 AN: 152040 Hom.: 21538 Cov.: 32 AF XY: 0.530 AC XY: 39405 AN XY: 74334

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.499

Alfa AF: 0.503 Hom.: 2119

Bravo AF: 0.531

Asia WGS AF: 0.688 AC: 2391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs2267922; hg19: chr19-18278766;