19-18156170-C-T

Position:

• chr19-18156170-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000222254.13(PIK3R2):​c.291C>T​(p.Pro97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,451,484 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (7 hom.)
• Consequence: PIK3R2 ENST00000222254.13 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.36

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-18156170-C-T is Benign according to our data. Variant chr19-18156170-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 468324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.36 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00707 (1077/152326) while in subpopulation AFR AF= 0.0251 (1043/41572). AF 95% confidence interval is 0.0238. There are 15 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1077 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R2	NM_005027.4	c.291C>T	p.Pro97=	synonymous_variant	2/16	ENST00000222254.13	NP_005018.2
PIK3R2	NR_073517.2	n.846C>T		non_coding_transcript_exon_variant	2/16
PIK3R2	NR_162071.1	n.846C>T		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13	c.291C>T	p.Pro97=	synonymous_variant	2/16	1	NM_005027.4	ENSP00000222254	P1
PIK3R2	ENST00000617130.5	c.291C>T	p.Pro97=	synonymous_variant, NMD_transcript_variant	2/15	1		ENSP00000477864
PIK3R2	ENST00000426902.5	c.291C>T	p.Pro97=	synonymous_variant, NMD_transcript_variant	1/15	2		ENSP00000395636
PIK3R2	ENST00000617642.2	c.291C>T	p.Pro97=	synonymous_variant, NMD_transcript_variant	2/14	5		ENSP00000484714

Frequencies

GnomAD3 genomes AF: 0.00708 AC: 1078 AN: 152208 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00168 AC: 122 AN: 72606 Hom.: 0 AF XY: 0.00133 AC XY: 53 AN XY: 39874

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000358

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000113

Gnomad OTH exome AF: 0.00128

GnomAD4 exome AF: 0.000631 AC: 820 AN: 1299158 Hom.: 7 Cov.: 31 AF XY: 0.000550 AC XY: 349 AN XY: 634070

Gnomad4 AFR exome AF: 0.0258

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000192

Gnomad4 OTH exome AF: 0.00175

GnomAD4 genome AF: 0.00707 AC: 1077 AN: 152326 Hom.: 15 Cov.: 33 AF XY: 0.00667 AC XY: 497 AN XY: 74488

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00527 Hom.: 1

Bravo AF: 0.00810

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 19, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.74
DANN	Benign	0.88

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: rs201655779; hg19: chr19-18266980;