19-18155196-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant names:

• chr19-18155196-C-CAAA
• rs34249019
• NM_005027.4:c.-423-243_-423-241dupAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005027.4(PIK3R2):​c.-423-243_-423-241dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00084 (3 hom., cov: 0)
• Consequence: PIK3R2 NM_005027.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000843 (92/109106) while in subpopulation SAS AF = 0.00221 (7/3162). AF 95% confidence interval is 0.00104. There are 3 homozygotes in GnomAd4. There are 48 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 92 AD gene.

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.-423-243_-423-241dupAAA		intron	N/A	NP_005018.2	O00459
	PIK3R2	NR_073517.2		n.133-243_133-241dupAAA		intron	N/A
	PIK3R2	NR_162071.1		n.133-243_133-241dupAAA		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_-423-260insAAA		intron	N/A	ENSP00000222254.6	O00459
	ENSG00000268173	ENST00000593731.1	TSL:2	n.-423-261_-423-260insAAA		intron	N/A	ENSP00000471914.1
	PIK3R2	ENST00000617130.6	TSL:1	n.-423-261_-423-260insAAA		intron	N/A	ENSP00000477864.2	A0A7I2U3A3

Frequencies

GnomAD3 genomes AF: 0.000852 AC: 93 AN: 109150 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00108

Gnomad AMI AF: 0.00130

Gnomad AMR AF: 0.00100

Gnomad ASJ AF: 0.000330

Gnomad EAS AF: 0.00100

Gnomad SAS AF: 0.00251

Gnomad FIN AF: 0.000270

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000679

Gnomad OTH AF: 0.000694

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

GnomAD4 genome AF: 0.000843 AC: 92 AN: 109106 Hom.: 3 Cov.: 0 AF XY: 0.000957 AC XY: 48 AN XY: 50154

African (AFR) AF: 0.00108 AC: 29 AN: 26886

American (AMR) AF: 0.00100 AC: 10 AN: 9966

Ashkenazi Jewish (ASJ) AF: 0.000330 AC: 1 AN: 3032

East Asian (EAS) AF: 0.00101 AC: 4 AN: 3968

South Asian (SAS) AF: 0.00221 AC: 7 AN: 3162

European-Finnish (FIN) AF: 0.000270 AC: 1 AN: 3702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.000679 AC: 38 AN: 55946

Other (OTH) AF: 0.000691 AC: 1 AN: 1448

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

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;