NM_005027.4:c.64_88dupGACCTGGAGCTGCTGCCCGGCGACG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_005027.4(PIK3R2):​c.64_88dupGACCTGGAGCTGCTGCCCGGCGACG​(p.Val30GlyfsTer48) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PIK3R2
NM_005027.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 21 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIK3R2NM_005027.4 linkc.64_88dupGACCTGGAGCTGCTGCCCGGCGACG p.Val30GlyfsTer48 frameshift_variant Exon 2 of 16 ENST00000222254.13 NP_005018.2 O00459
PIK3R2NR_073517.2 linkn.619_643dupGACCTGGAGCTGCTGCCCGGCGACG non_coding_transcript_exon_variant Exon 2 of 16
PIK3R2NR_162071.1 linkn.619_643dupGACCTGGAGCTGCTGCCCGGCGACG non_coding_transcript_exon_variant Exon 2 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIK3R2ENST00000222254.13 linkc.64_88dupGACCTGGAGCTGCTGCCCGGCGACG p.Val30GlyfsTer48 frameshift_variant Exon 2 of 16 1 NM_005027.4 ENSP00000222254.6 O00459
ENSG00000268173ENST00000593731.1 linkn.64_88dupGACCTGGAGCTGCTGCCCGGCGACG non_coding_transcript_exon_variant Exon 2 of 25 2 ENSP00000471914.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 Uncertain:1
Jan 28, 2020
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2043673731; hg19: chr19-18266751; API