19-18155196-CAAAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chr19-18155196-C-CAA
• rs34249019
• NM_005027.4:c.-423-242_-423-241dupAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005027.4(PIK3R2):​c.-423-242_-423-241dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.029 (143 hom., cov: 0)
• Consequence: PIK3R2 NM_005027.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.181
• Publications: 0 publications found

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]

PIK3R2 Gene-Disease associations (from GenCC):

• megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Illumina, G2P
• overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000268173 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-18155196-C-CAA is Benign according to our data. Variant chr19-18155196-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1267586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005027.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R2	NM_005027.4	MANE Select	c.-423-242_-423-241dupAA		intron	N/A	NP_005018.2	O00459
	PIK3R2	NR_073517.2		n.133-242_133-241dupAA		intron	N/A
	PIK3R2	NR_162071.1		n.133-242_133-241dupAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R2	ENST00000222254.13	TSL:1 MANE Select	c.-423-261_-423-260insAA		intron	N/A	ENSP00000222254.6	O00459
	ENSG00000268173	ENST00000593731.1	TSL:2	n.-423-261_-423-260insAA		intron	N/A	ENSP00000471914.1
	PIK3R2	ENST00000617130.6	TSL:1	n.-423-261_-423-260insAA		intron	N/A	ENSP00000477864.2	A0A7I2U3A3

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 3155 AN: 108690 Hom.: 143 Cov.: 0

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.00389

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0189

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.0461

Gnomad FIN AF: 0.00946

Gnomad MID AF: 0.0282

Gnomad NFE AF: 0.00946

Gnomad OTH AF: 0.0202

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

GnomAD4 genome AF: 0.0291 AC: 3162 AN: 108646 Hom.: 143 Cov.: 0 AF XY: 0.0298 AC XY: 1490 AN XY: 49936

African (AFR) AF: 0.0798 AC: 2141 AN: 26840

American (AMR) AF: 0.0169 AC: 168 AN: 9932

Ashkenazi Jewish (ASJ) AF: 0.0189 AC: 57 AN: 3014

East Asian (EAS) AF: 0.0124 AC: 49 AN: 3952

South Asian (SAS) AF: 0.0465 AC: 147 AN: 3160

European-Finnish (FIN) AF: 0.00946 AC: 35 AN: 3698

Middle Eastern (MID) AF: 0.0315 AC: 7 AN: 222

European-Non Finnish (NFE) AF: 0.00946 AC: 526 AN: 55610

Other (OTH) AF: 0.0201 AC: 29 AN: 1446

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34249019; hg19: chr19-18266006;