Variant chr2-71202558-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020459.1(PAIP2B):c.32C>T(p.Pro11Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PAIP2B
NM_020459.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

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]

PAIP2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103001624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAIP2B	NM_020459.1 linkuse as main transcript	c.32C>T	p.Pro11Leu	missense_variant	2/4	ENST00000244221.9	NP_065192.1	Q9ULR5
PAIP2B	XM_011532842.4 linkuse as main transcript	c.95C>T	p.Pro32Leu	missense_variant	2/4		XP_011531144.1
PAIP2B	XM_005264310.5 linkuse as main transcript	c.32C>T	p.Pro11Leu	missense_variant	3/5		XP_005264367.1	Q9ULR5
PAIP2B	XM_005264311.5 linkuse as main transcript	c.32C>T	p.Pro11Leu	missense_variant	2/4		XP_005264368.1	Q9ULR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAIP2B	ENST00000244221.9 linkuse as main transcript	c.32C>T	p.Pro11Leu	missense_variant	2/4	1	NM_020459.1	ENSP00000244221.8		Q9ULR5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249092

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135144

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461330

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.32C>T (p.P11L) alteration is located in exon 2 (coding exon 1) of the PAIP2B gene. This alteration results from a C to T substitution at nucleotide position 32, causing the proline (P) at amino acid position 11 to be replaced by a leucine (L). 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

0.080

BayesDel_addAF

Benign

0.0071

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

M_CAP

Benign

0.0093

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.35

Sift

Uncertain

0.0040

Sift4G

Benign

0.56

Polyphen

0.33

Vest4

0.23

MutPred

0.17

Loss of glycosylation at P11 (P = 0.0515);

MVP

0.36

MPC

0.037

ClinPred

0.99

GERP RS

5.1

Varity_R

0.23

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over