17-8881775-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142633.3(PIK3R5):c.2299+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,612,678 control chromosomes in the GnomAD database, including 49,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4737 hom., cov: 32)
  • Exomes 𝑓: 0.24 (45238 hom.)
• Consequence: PIK3R5 NM_001142633.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.39

Genes affected

PIK3R5 (HGNC:30035): (phosphoinositide-3-kinase regulatory subunit 5) Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. This gene encodes the 101 kD regulatory subunit of the class I PI3K gamma complex, which is a dimeric enzyme, consisting of a 110 kD catalytic subunit gamma and a regulatory subunit of either 55, 87 or 101 kD. This protein recruits the catalytic subunit from the cytosol to the plasma membrane through high-affinity interaction with G-beta-gamma proteins. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found. [provided by RefSeq, Oct 2011]

LOC124903919 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-8881775-C-T is Benign according to our data. Variant chr17-8881775-C-T is described in ClinVar as [Benign]. Clinvar id is 257556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8881775-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R5	NM_001142633.3	c.2299+13G>A		intron_variant		ENST00000447110.6
LOC124903919	XR_007065610.1	n.924-2791C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R5	ENST00000447110.6	c.2299+13G>A		intron_variant		5	NM_001142633.3	P4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36354 AN: 151772 Hom.: 4733 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.241

GnomAD3 exomes AF: 0.211 AC: 52885 AN: 250808 Hom.: 6310 AF XY: 0.207 AC XY: 28019 AN XY: 135574

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.000652

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.242 AC: 353644 AN: 1460788 Hom.: 45238 Cov.: 32 AF XY: 0.238 AC XY: 172662 AN XY: 726762

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.000428

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.239 AC: 36372 AN: 151890 Hom.: 4737 Cov.: 32 AF XY: 0.230 AC XY: 17098 AN XY: 74242

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.239

Alfa AF: 0.249 Hom.: 888

Bravo AF: 0.250

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Ataxia with oculomotor apraxia type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.6
Dann	Benign	0.47

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: rs9902600; hg19: chr17-8785092;