Variant chr21-44114188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005049.3(PWP2):c.236C>T(p.Ala79Val) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000057 ( 1 hom., cov: 6)

Exomes 𝑓: 0.00014 ( 24 hom. )

Failed GnomAD Quality Control

Consequence

PWP2
NM_005049.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.02

Variant links:

Genes affected

PWP2 (HGNC:9711): (PWP2 small subunit processome component) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and ribosomal small subunit assembly. Predicted to be located in nucleoplasm. Predicted to be part of Pwp2p-containing subcomplex of 90S preribosome and small-subunit processome. [provided by Alliance of Genome Resources, Apr 2022]

PWP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PWP2	NM_005049.3 linkuse as main transcript	c.236C>T	p.Ala79Val	missense_variant	4/21	ENST00000291576.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PWP2	ENST00000291576.12 linkuse as main transcript	c.236C>T	p.Ala79Val	missense_variant	4/21	1	NM_005049.3	P1
PWP2	ENST00000456705.1 linkuse as main transcript	c.226+341C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

70720

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000453

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000142

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

250574

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000706

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000142

AC:

AN:

395010

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

206880

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00443

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000464

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000566

AC:

AN:

70720

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34010

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000453

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000142

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000133

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Oct 05, 2021

The c.236C>T (p.A79V) alteration is located in exon 4 (coding exon 4) of the PWP2 gene. This alteration results from a C to T substitution at nucleotide position 236, causing the alanine (A) at amino acid position 79 to be replaced by a valine (V). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.089

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.75

MVP

0.40

MPC

0.56

ClinPred

0.79

GERP RS

4.6

Varity_R

0.53

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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