NM_005027.4:c.-423-242_-423-241delAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005027.4(PIK3R2):​c.-423-242_-423-241delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000064 (0 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: Uncertain_significance. The variant received 0 ACMG points.

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_-423-241delAA		intron	N/A	NP_005018.2	O00459
	PIK3R2	NR_073517.2		n.133-242_133-241delAA		intron	N/A
	PIK3R2	NR_162071.1		n.133-242_133-241delAA		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_-423-259delAA		intron	N/A	ENSP00000222254.6	O00459
	ENSG00000268173	ENST00000593731.1	TSL:2	n.-423-260_-423-259delAA		intron	N/A	ENSP00000471914.1
	PIK3R2	ENST00000617130.6	TSL:1	n.-423-260_-423-259delAA		intron	N/A	ENSP00000477864.2	A0A7I2U3A3

Frequencies

GnomAD3 genomes AF: 0.0000640 AC: 7 AN: 109298 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000372

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000541

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000178

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000640 AC: 7 AN: 109298 Hom.: 0 Cov.: 0 AF XY: 0.0000796 AC XY: 4 AN XY: 50234

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000372 AC: 1 AN: 26898

American (AMR) AF: 0.000301 AC: 3 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: 0.000541 AC: 2 AN: 3698

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

European-Non Finnish (NFE) AF: 0.0000178 AC: 1 AN: 56032

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18

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

Other links and lift over

dbSNP: rs34249019; hg19: chr19-18266006;