Variant 10-132404831-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138499.4(PWWP2B):c.331G>A(p.Ala111Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000672 in 817,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

PWWP2B
NM_138499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.289

Variant links:

Genes affected

PWWP2B (HGNC:25150): (PWWP domain containing 2B) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PWWP2B links:

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=0.0495708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PWWP2B	NM_138499.4 linkuse as main transcript	c.331G>A	p.Ala111Thr	missense_variant	2/3	ENST00000305233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PWWP2B	ENST00000305233.6 linkuse as main transcript	c.331G>A	p.Ala111Thr	missense_variant	2/3	1	NM_138499.4	P1	Q6NUJ5-1
PWWP2B	ENST00000631148.2 linkuse as main transcript	c.331G>A	p.Ala111Thr	missense_variant	2/3	5			Q6NUJ5-2

Frequencies

GnomAD3 genomes

AF:

0.0000287

AC:

AN:

104606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000533

AC:

AN:

187588

Hom.:

AF XY:

0.0000857

AC XY:

AN XY:

105022

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.0000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000120

Gnomad NFE exome

AF:

0.0000710

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000729

AC:

AN:

713328

Hom.:

Cov.:

AF XY:

0.0000906

AC XY:

AN XY:

364332

show subpopulations

Gnomad4 AFR exome

AF:

0.000104

Gnomad4 AMR exome

AF:

0.0000614

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.0000718

Gnomad4 FIN exome

AF:

0.000183

Gnomad4 NFE exome

AF:

0.0000686

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.0000287

AC:

AN:

104606

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

48338

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000439

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

May 17, 2023

The c.331G>A (p.A111T) alteration is located in exon 2 (coding exon 2) of the PWWP2B gene. This alteration results from a G to A substitution at nucleotide position 331, causing the alanine (A) at amino acid position 111 to be replaced by a threonine (T). 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

0.073

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.6

DANN

Benign

0.94

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.62

Sift4G

Benign

0.46

T;T

Polyphen

0.024

.;B

Vest4

0.083

MutPred

0.28

Gain of glycosylation at A111 (P = 0.0012);Gain of glycosylation at A111 (P = 0.0012);

MVP

0.043

MPC

0.57

ClinPred

0.0098

GERP RS

2.7

Varity_R

0.025

gMVP

0.31

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