2-71202531-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020459.1(PAIP2B):​c.59G>A​(p.Gly20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PAIP2B
NM_020459.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.446
Variant links:
Genes affected
PAIP2B (HGNC:29200): (poly(A) binding protein interacting protein 2B) Most mRNAs, except for histones, contain a 3-prime poly(A) tail. Poly(A)-binding protein (PABP; see MIM 604679) enhances translation by circularizing mRNA through its interaction with the translation initiation factor EIF4G1 (MIM 600495) and the poly(A) tail. Various PABP-binding proteins regulate PABP activity, including PAIP1 (MIM 605184), a translational stimulator, and PAIP2A (MIM 605604) and PAIP2B, translational inhibitors (Derry et al., 2006 [PubMed 17381337]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.025422007).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAIP2BNM_020459.1 linkc.59G>A p.Gly20Glu missense_variant Exon 2 of 4 ENST00000244221.9 NP_065192.1 Q9ULR5
PAIP2BXM_011532842.4 linkc.122G>A p.Gly41Glu missense_variant Exon 2 of 4 XP_011531144.1
PAIP2BXM_005264310.5 linkc.59G>A p.Gly20Glu missense_variant Exon 3 of 5 XP_005264367.1 Q9ULR5
PAIP2BXM_005264311.5 linkc.59G>A p.Gly20Glu missense_variant Exon 2 of 4 XP_005264368.1 Q9ULR5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAIP2BENST00000244221.9 linkc.59G>A p.Gly20Glu missense_variant Exon 2 of 4 1 NM_020459.1 ENSP00000244221.8 Q9ULR5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249284
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135238
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461536
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727056
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000450
Hom.:
0
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 02, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.59G>A (p.G20E) alteration is located in exon 2 (coding exon 1) of the PAIP2B gene. This alteration results from a G to A substitution at nucleotide position 59, causing the glycine (G) at amino acid position 20 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
11
DANN
Uncertain
0.98
DEOGEN2
Benign
0.013
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.025
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.69
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.45
N
REVEL
Benign
0.11
Sift
Uncertain
0.019
D
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.049
MutPred
0.15
Gain of solvent accessibility (P = 0.0837);
MVP
0.17
MPC
0.041
ClinPred
0.16
T
GERP RS
-1.2
Varity_R
0.075
gMVP
0.39

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs747007531; hg19: chr2-71429661; API