rs2242375

Positions:

• chr17-8803133-T-C
• chr17-8803133-T-G

Variant summary

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

The NM_001010855.4(PIK3R6):​c.*140A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,117,060 control chromosomes in the GnomAD database, including 109,749 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 0.35 (11458 hom., cov: 32)
  • Exomes 𝑓: 0.45 (98291 hom.)
• Consequence: PIK3R6 NM_001010855.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

Genes affected

PIK3R6 (HGNC:27101): (phosphoinositide-3-kinase regulatory subunit 6) Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regulatory subunit 5 gene which is located adjacent to this gene on chromosome 7. The orthologous protein in the mouse binds to both the catalytic subunit and to G(beta/gamma), and mediates activation of the kinase subunit downstream of G protein-coupled receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

PIK3R6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R6	NM_001010855.4	c.*140A>G		3_prime_UTR_variant	20/20	ENST00000619866.5	NP_001010855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R6	ENST00000619866	c.*140A>G		3_prime_UTR_variant	20/20	5	NM_001010855.4	ENSP00000480157.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53222 AN: 151964 Hom.: 11447 Cov.: 32

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.447 AC: 430898 AN: 964978 Hom.: 98291 Cov.: 13 AF XY: 0.447 AC XY: 216772 AN XY: 485448

Gnomad4 AFR exome AF: 0.0822

Gnomad4 AMR exome AF: 0.396

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.350 AC: 53236 AN: 152082 Hom.: 11458 Cov.: 32 AF XY: 0.357 AC XY: 26496 AN XY: 74322

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.351

Alfa AF: 0.432 Hom.: 10260

Bravo AF: 0.326

Asia WGS AF: 0.365 AC: 1267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.67

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: rs2242375; hg19: chr17-8706451; COSMIC: COSV61005334; COSMIC: COSV61005334;