NM_005027.4:c.-423-252_-423-241delAAAAAAAAAAAA

Variant names:

• chr19-18155196-CAAAAAAAAAAAA-C
• rs34249019
• NM_005027.4:c.-423-252_-423-241delAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_005027.4(PIK3R2):​c.-423-252_-423-241delAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000037 (0 hom., cov: 0)
• Consequence: PIK3R2 NM_005027.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000366 (4/109306) while in subpopulation AFR AF = 0.000149 (4/26898). AF 95% confidence interval is 0.0000506. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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.-423-252_-423-241delAAAAAAAAAAAA		intron	N/A	NP_005018.2	O00459
	PIK3R2	NR_073517.2		n.133-252_133-241delAAAAAAAAAAAA		intron	N/A
	PIK3R2	NR_162071.1		n.133-252_133-241delAAAAAAAAAAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R2	ENST00000222254.13	TSL:1 MANE Select	c.-423-260_-423-249delAAAAAAAAAAAA		intron	N/A	ENSP00000222254.6	O00459
	ENSG00000268173	ENST00000593731.1	TSL:2	n.-423-260_-423-249delAAAAAAAAAAAA		intron	N/A	ENSP00000471914.1
	PIK3R2	ENST00000617130.6	TSL:1	n.-423-260_-423-249delAAAAAAAAAAAA		intron	N/A	ENSP00000477864.2	A0A7I2U3A3

Frequencies

GnomAD3 genomes AF: 0.0000366 AC: 4 AN: 109306 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000366 AC: 4 AN: 109306 Hom.: 0 Cov.: 0 AF XY: 0.0000398 AC XY: 2 AN XY: 50238

African (AFR) AF: 0.000149 AC: 4 AN: 26898

American (AMR) AF: 0.00 AC: 0 AN: 9974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3034

East Asian (EAS) AF: 0.00 AC: 0 AN: 3990

South Asian (SAS) AF: 0.00 AC: 0 AN: 3198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56036

Other (OTH) AF: 0.00 AC: 0 AN: 1446

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

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;