19-18155862-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005027.4(PIK3R2):c.-18C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,531,578 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (3 hom.)
• Consequence: PIK3R2 NM_005027.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.123

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-18155862-C-T is Benign according to our data. Variant chr19-18155862-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000505 (77/152352) while in subpopulation EAS AF= 0.0129 (67/5186). AF 95% confidence interval is 0.0104. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R2	NM_005027.4	c.-18C>T		5_prime_UTR_variant	2/16	ENST00000222254.13
PIK3R2	NR_073517.2	n.538C>T		non_coding_transcript_exon_variant	2/16
PIK3R2	NR_162071.1	n.538C>T		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R2	ENST00000222254.13	c.-18C>T		5_prime_UTR_variant	2/16	1	NM_005027.4	P1
PIK3R2	ENST00000617130.5	c.-18C>T		5_prime_UTR_variant, NMD_transcript_variant	2/15	1
PIK3R2	ENST00000426902.5	c.-18C>T		5_prime_UTR_variant, NMD_transcript_variant	1/15	2
PIK3R2	ENST00000617642.2	c.-18C>T		5_prime_UTR_variant, NMD_transcript_variant	2/14	5

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000957 AC: 131 AN: 136902 Hom.: 1 AF XY: 0.000873 AC XY: 64 AN XY: 73340

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000445

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0120

Gnomad SAS exome AF: 0.000346

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.000253

GnomAD4 exome AF: 0.000381 AC: 526 AN: 1379226 Hom.: 3 Cov.: 30 AF XY: 0.000377 AC XY: 256 AN XY: 678950

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0114

Gnomad4 SAS exome AF: 0.000689

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000617

Gnomad4 OTH exome AF: 0.000210

GnomAD4 genome AF: 0.000505 AC: 77 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.000550 AC XY: 41 AN XY: 74498

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000855 Hom.: 0

Bravo AF: 0.000737

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	11
Dann	Benign	0.92

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: rs148245146; hg19: chr19-18266672;