rs587777624
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_005027.4(PIK3R2):c.1202T>C(p.Leu401Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 30)
Consequence
PIK3R2
NM_005027.4 missense
NM_005027.4 missense
Scores
14
3
1
Clinical Significance
Conservation
PhyloP100: 7.83
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 Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.991
PP5
?
Variant 19-18163059-T-C is Pathogenic according to our data. Variant chr19-18163059-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 143990.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3R2 | NM_005027.4 | c.1202T>C | p.Leu401Pro | missense_variant | 10/16 | ENST00000222254.13 | |
PIK3R2 | NR_073517.2 | n.1757T>C | non_coding_transcript_exon_variant | 10/16 | |||
PIK3R2 | NR_162071.1 | n.1540T>C | non_coding_transcript_exon_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3R2 | ENST00000222254.13 | c.1202T>C | p.Leu401Pro | missense_variant | 10/16 | 1 | NM_005027.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
Cov.:
30
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;H
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of stability (P = 0.0027);Loss of stability (P = 0.0027);Loss of stability (P = 0.0027);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at